Anthranilamide and 2-amino-heteroarene-carboxamide compounds

ABSTRACT

Compounds of formula I 
                         
processes for their preparation, their use as pharmaceuticals and to pharmaceutical compositions comprising them.

PRIORITY TO RELATED APPLICATIONS

This application claims the benefit of European Application No.06101366.0, filed Feb. 7, 2006, which is hereby incorporated byreference in its entirety.

The present invention relates to novel anthranilamide and2-amino-heteroarene-carboxamide derivatives, processes for theirpreparation, their use as pharmaceuticals and to pharmaceuticalcompositions comprising them.

More particularly, the present invention provides in a first aspect acompound of formula I

whereinR¹, R², R⁴ and R⁵ are independently hydrogen, C₁-C₆alkyl, C₁-C₆alkoxy orhalogen;R³ is C₁-C₆alkyl, halogen-C₁-C₆alkyl, C₃-C₆cycloalkyl, Si(C₁-C₆alkyl)₃,—OR¹², wherein R¹² is C₁-C₆alkyl, halogen-C₁-C₆alkyl, C₃-C₆cycloalkyl,phenyl, benzyl or S(O)₂—C₁-C₆alkyl, or pentafluorosulfuranyl; orR² and R³ taken together with the carbon atoms they are attached to forma 5- or 6-membered carbocyclic ring or a 5- or 6-membered heterocyclicring containing one or two heteroatoms selected from N, O or S;R⁶ is hydrogen or C₁-C₆alkyl;R⁷ and R⁸ are independently hydrogen, C₁-C₆alkyl, hydroxy or halogen;R⁹ is hydrogen, C₁-C₆alkyl, C₂-C₆alkenyl, halogen-C₁-C₆alkyl,heterocyclyl, heteroaryl, phenyl, naphthyl, —OR¹³, wherein R¹³ isC₁-C₆alkyl or phenyl, —NR¹⁴R¹⁵, wherein R¹⁴ and R¹⁵ independently arehydrogen, C₁-C₆alkyl or phenyl, or —C(O)—OR¹⁶, wherein R¹⁶ is hydrogenor C₁-C₆alkyl;R¹⁰ and R¹¹ are independently hydrogen, halogen, C₁-C₆alkyl, COR whereinR is C₁-C₆alkyl, C₁-C₆alkoxy or C₃-C₆cycloalkyl, S(O)₂—C₁-C₆alkyl,C₃-C₆cycloalkyl, or phenyl; or together are C₁-C₆alkylene;A is CR¹⁷ or N, wherein R¹⁷ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy or C₂-C₆alkenyl;B is CR¹⁸ or N, wherein R¹⁸ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy or C₂-C₆alkenyl;D is CR¹⁹ or N, wherein R¹⁹ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy, C₂-C₆alkenyl or phenyl;E is CR²⁰ or N, wherein R²⁰ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy or C₂-C₆alkenyl; orE is CR²⁰ and -A-B-D- is —N—O—, —NR²¹—N—, —S—N—, —S—CH— or —CH—S—,wherein R²¹ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy orC₂-C₆alkenyl; orE is N and -A-B-D- is —N—O—, —S—N—, —S—CH—, —CH—CH— or —CH—S—; orE is S and -A-B-D- is —CH—CH—; andn is 1, 2 or 3;and all pharmaceutically acceptable salts thereof.

The compounds of formula I may bear substituents within their structure,e.g. may bear appropriate alkyl, alkylene or phenyl substituents, e.g.alkyl and alkylene may be substituted by one to thirteen substituentsselected from hydroxy, halogen, C₃-C₆cycloalkyl, cyano, COOH,COOC₁-C₆alkyl and C₁-C₆alkoxy; phenyl may be substituted by one to fivegroups independently selected from C₁-C₆alkyl, C₁-C₆alkoxy,halogen-C₁-C₆alkyl, halogen-C₁-C₆alkoxy, amino and halogen.

Phenyl and heteroaryl may be annulated with a saturated or unsaturatedmoiety to form a bicyclic group.

Examples for alkyl, alone or in combination with other groups, includebranched or straight-chain monovalent saturated aliphatic hydrocarbonradicals of one to six carbon atoms, e.g. methyl, ethyl, propyl,isopropyl, butyl, isobutyl, tert-butyl, the isomeric pentyls and theisomeric hexyls.

Examples for alkenyl, alone or in combination, include straight-chain orbranched hydrocarbon radicals comprising an olefinic bond and up to 6,e.g., up to 4 carbon atoms, e.g. ethenyl, 1-propenyl, 2-propenyl,isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl and isobutenyl. Examplesfor aryl include phenyl and naphthyl.

Examples for amino include amino, alkylamino, cycloalkylamino,dialkylamino, hydroxyalkylamino, carboxyalkylamino, acylamino,sulfonylamino, acetidin-1-yl and pyrrolidin-1-yl. Heterocyclic groupsmay be saturated or unsaturated and may contain one or more additionalheteroatoms, e.g. nitrogen, oxygen or sulfur.

Examples for an unsaturated heterocyclic group include a heteroarylgroup like pyridinyl, pyridazinyl, pyrimidinyl, thiazolyl, oxazolyl,isothiazolyl, isoxazolyl, thiophenyl, furanyl, pyrazolyl, e.g.aminopyridinyl, aminopyridazinyl, aminopyrimidinyl, aminothiophenyl,aminopyrazolyl, aminothiazolyl, aminoisothiazolyl, aminoisoxazolyl, e.g.2-aminopyridin-3-yl, 3-aminopyridin-2-yl, 4-aminopyridin-3-yl,3-aminopyridin-4-yl, 3-aminopyrazin-2-yl, 4-aminopyridazin-3-yl,5-aminopyridazin-4-yl, 3-aminopyridazin-4-yl, 4-aminopyrimidin-5-yl,5-aminopyrimidin-4-yl, 5-aminothiazol-4-yl, 5-aminoisothiazol-4-yl and3-aminoisoxazol-4-yl, 2-aminothiophen-3-yl, 3-aminothiophen-2-yl,3-aminothiophen-4-yl, 5-aminopyrazol-4-yl and may be unsubstituted orsubstituted by one to three substituents selected from halogen, alkyl,halogenalkyl, cycloalkyl which may again be unsubstituted or substitutedby one or more of the above mentioned substituents.

Examples for halogen include fluorine, chlorine, bromine, iodine.

The term halogen-C₁-C₆alkyl refers to C₁-C₆alkyl groups as defined abovewherein at least one of the hydrogen atoms of the C₁-C₆alkyl group isreplaced by a halogen atom, e.g. fluoro or chloro. Examples ofhalogenated C₁-C₆alkyl groups include trifluoromethyl, difluoromethyl,fluoromethyl and chlorodifluoromethyl.

The term halogen-C₁-C₆alkoxy refers to C₁-C₆alkoxy groups as definedabove wherein at least one of the hydrogen atoms of the C₁-C₆alkoxygroup is replaced by a halogen atom, e.g. fluoro or chloro. Examples ofhalogenated C₁-C₆alkyl groups include trifluoromethoxy, difluoromethoxy,fluoromethoxy and chlorodifluoromethoxy.

The term C₁-C₆alkoxy-halogen-C₁-C₆alkyl refers to halogen-C₁-C₆alkylgroups as defined above wherein at least one of the hydrogen atoms ofthe halogen-C₁-C₆alkyl group is replaced by an alkoxy group. An exampleof a C₁-C₆alkoxy-halogen-C₁-C₆alkyl group is2,2,2-trifluoro-1-methoxy-1-trifluoromethyl-ethyl.

Compounds of the invention exist in free or salt, e.g. acid additionsalt form. The invention is to be understood as including the compoundsof formula I in free as well as in salt form, e.g. as hydrochloride,sulfate or sodium salt.

In one embodiment the present invention provides a compound of formula Iwherein R¹ is hydrogen or halogen. In another embodiment the presentinvention provides a compound of formula I wherein R¹ is hydrogen orchlorine. In still another embodiment the present invention provides acompound of formula I wherein R¹ is hydrogen.

In one embodiment the present invention provides a compound of formula Iwherein R² is hydrogen or halogen. In another embodiment the presentinvention provides a compound of formula I wherein R² is hydrogen,fluorine or chlorine. In still another embodiment the present inventionprovides a compound of formula I wherein R² is hydrogen.

In one embodiment the present invention provides a compound of formula Iwherein R³ is C₁-C₆alkyl, halogen-C₁-C₆alkyl, C₃-C₆cycloalkyl,C₃-C₆cycloalkyl which is substituted by one to eleven halogen orC₁-C₆alkoxy, Si(C₁-C₆alkyl)₃, —OR¹², wherein R¹² is C₁-C₆alkyl which isunsubstituted or substituted by one to six substituents selected fromhalogen, COOC₁-C₆alkyl, hydroxy, C₃-C₆cycloalkyl and phenyl which isunsubstituted or substituted by halogen or cyano; phenyl; orS(O)₂—C₁-C₆alkyl; or pentafluorosulphuranyl. In another embodiment thepresent invention provides a compound of formula I wherein R³ isC₁-C₆alkyl, halogen-C₁-C₆alkyl, C₃-C₆cycloalkyl, C₃-C₆cycloalkyl whichis substituted by one to eleven halogen or C₁-C₆alkoxy, —OR¹², whereinR¹² is C₁-C₆alkyl which is unsubstituted or substituted by one to sixsubstituents selected from halogen, hydroxy and C₃-C₆cycloalkyl; phenyl;or S(O)₂—C₁-C₆alkyl; or pentafluorosulphuranyl. In still anotherembodiment the present invention provides a compound of formula Iwherein R³ is C₁-C₆alkyl, halogen-C₁-C₆alkyl, C₃-C₆cycloalkyl,C₃-C₆cycloalkyl which is substituted by one to eleven halogen orC₁-C₆alkoxy, —OR¹², wherein R¹² is C₁-C₆alkyl which is unsubstituted orsubstituted by one to six halogen. In still another embodiment thepresent invention provides a compound of formula I wherein R³ is CH₃,CH₂CH₃, C(CH₃)₃, CH(CH₃)₂, CF₃, CF(CF₃)₂, CF₂CF₃, cyclopropyl,cyclobutyl, cyclopentyl, 1-fluorocyclopropyl, 1-fluorocyclobutyl,1-methoxycyclopropyl, 1-methoxycyclobutyl, OC(CH₃)₃, OCF₃, OCF₂CHF₂,OCH₂COOCH₃, OCH₂CH(OH)CF₃, OCH₂cyclopropyl, O-4-fluorobenzyl,O-4-cyanobenzyl, phenoxy, OS(O)₂CH₃, Si(CH₃)₃ or SF₅. In still anotherembodiment the present invention provides a compound of formula Iwherein R³ is CH₃, CH₂CH₃, C(CH₃)₃, CF₃, CF(CF₃)₂, CF₂CF₃, cyclopropyl,cyclobutyl, cyclopentyl, 1-fluorocyclopropyl, 1-fluorocyclobutyl,1-methoxycyclopropyl, 1-methoxycyclobutyl, OC(CH₃)₃, OCF₃ or OCF₂CHF₂.In another embodiment the present invention provides a compound offormula I wherein R³ is unsubstituted C₁-C₆alkyl, C₁-C₆alkyl which issubstituted by halogen or unsubstituted C₃-C₆cycloalkyl. In stillanother embodiment the present invention provides a compound of formulaI wherein R³ is CH₃, CH₂CH₃, C(CH₃)₃, CH(CH₃)₂, CF₃, CF(CF₃)₂, CF₂CF₃,cyclopropyl, cyclobutyl or cyclopentyl.

In one embodiment the present invention provides a compound of formula Iwherein R⁴ is hydrogen.

In one embodiment the present invention provides a compound of formula Iwherein R⁵ is hydrogen.

In one embodiment the present invention provides a compound of formula Iwherein R⁶ is hydrogen.

In one embodiment the present invention provides a compound of formula Iwherein R⁷ is hydrogen, hydroxy or halogen.

In one embodiment the present invention provides a compound of formula Iwherein R⁸ is hydrogen, hydroxy or halogen.

In one embodiment the present invention provides a compound of formula Iwherein R⁷ is hydrogen or halogen and R⁸ is hydrogen, hydroxy orhalogen. In another embodiment the present invention provides a compoundof formula I wherein R⁷ is hydrogen and R⁸ is hydrogen or R⁷ is hydrogenand R⁸ is hydroxy or halogen. In another embodiment the presentinvention provides a compound of formula I wherein R⁷ is halogen and R⁸is halogen.

In one embodiment the present invention provides a compound of formula Iwherein R⁹ is hydrogen, heteroaryl which is unsubstituted or substitutedby one to five substituents selected from halogen, C₁-C₆alkyl,halogen-C₁-C₆alkyl and phenyl, phenyl which is unsubstituted orsubstituted by one to five substituents selected from halogen,C₁-C₆alkyl, halogen-C₁-C₆alkyl and halogen-C₁-C₆alkoxy, naphthyl, —OR¹³,wherein R¹³ is C₁-C₆alkyl or phenyl, or —NR⁴R⁵, wherein R¹⁴ and R¹⁵independently are hydrogen, C₁-C₆alkyl or phenyl which is unsubstitutedor substituted by halogen. In another embodiment the present inventionprovides a compound of formula I wherein R⁹ is hydrogen, heteroarylwhich is substituted by one to three substituents selected from halogen,C₁-C₆alkyl, halogen-C₁-C₆alkyl and phenyl, phenyl which is unsubstitutedor substituted by one to three substituents selected from halogen,C₁-C₆alkyl, halogen-C₁-C₆alkyl and halogen-C₁-C₆alkoxy, naphthyl, —OR¹³,wherein R¹³ is phenyl, or —NR¹⁴R¹⁵, wherein R¹⁴ and R¹⁵ independentlyare hydrogen, C₁-C₆alkyl or phenyl which is substituted by halogen.

In one embodiment the present invention provides a compound of formula Iwherein R⁹ is heteroaryl selected from

wherein R²⁵, R²⁶ and R²⁷ independently are hydrogen, halogen,C₁-C₆alkyl, halogen-C₁-C₆alkyl or phenyl,R²⁸ and R³² are hydrogen, halogen, C₁-C₆alkyl, halogen-C₁-C₆alkyl orphenyl, andR²⁹, R³⁰ and R³¹ independently are hydrogen, halogen, C₁-C₆alkyl,halogen-C₁-C₆alkyl or phenyl.

In another embodiment the present invention provides a compound offormula I wherein R⁹ is

whereinR²⁵ is hydrogen, C₁-C₆alkyl, halogen-C₁-C₆alkyl or phenyl;R²⁶ is hydrogen or halogen;R²⁷ is hydrogen, C₁-C₆alkyl or halogen-C₁-C₆alkyl.

In another embodiment the present invention provides a compound offormula I wherein R⁹ is

wherein R²⁸ is halogen-C₁-C₆alkyl.

In another embodiment the present invention provides a compound offormula I wherein R⁹ is

whereinR²⁹ is hydrogen or halogen-C₁-C₆alkyl;R³⁰ is hydrogen, halogen or halogen-C₁-C₆alkyl; andR³¹ is hydrogen or halogen-C₁-C₆alkyl.

In another embodiment the present invention provides a compound offormula I wherein R⁹ is

wherein R³² is halogen.

In one embodiment the present invention provides a compound of formula Iwherein R⁹ is hydrogen.

In one embodiment the present invention provides a compound of formula Iwherein R⁹ is phenyl which is unsubstituted or substituted by one tofive substituents selected from halogen, C₁-C₆alkyl, halogen-C₁-C₆alkyland halogen-C₁-C₆alkoxy. In another embodiment the present inventionprovides a compound of formula I wherein R⁹ is phenyl which isunsubstituted or substituted by one to three substituents selected fromhalogen, C₁-C₆alkyl, halogen-C₁-C₆alkyl and halogen-C₁-C₆alkoxy.

In still another embodiment the present invention provides a compound offormula I wherein R⁹ is a group

wherein R²², R²³ and R²⁴ independently are hydrogen, halogen,C₁-C₆alkyl, halogen-C₁-C₆alkyl or halogen-C₁-C₆alkoxy. In still anotherembodiment the present invention provides a compound of formula Iwherein R⁹ is a group (ph) wherein R²² is hydrogen or halogen; R²³ ishydrogen, halogen, halogen-C₁-C₆alkyl or halogen-C₁-C₆alkoxy; and R²⁴ ishydrogen, halogen, C₁-C₆alkyl, halogen-C₁-C₆alkyl orhalogen-C₁-C₆alkoxy. In still another embodiment the present inventionprovides a compound of formula I wherein R⁹ is a group (ph) wherein R²²is hydrogen; R²³ is hydrogen, halogen-C₁-C₆alkyl or halogen-C₁-C₆alkoxy;and R²⁴ is hydrogen or C₁-C₆alkyl.

In one embodiment the present invention provides a compound of formula Iwherein R⁹ is naphthyl.

In one embodiment the present invention provides a compound of formula Iwherein R⁹ is —OR¹³, wherein R¹³ is C₁-C₆alkyl or phenyl. In anotherembodiment the present invention provides a compound of formula Iwherein R⁹ is —OR¹³, wherein R¹³ is phenyl. In one embodiment thepresent invention provides a compound of formula I wherein R⁹ is—NR¹⁴R¹⁵, wherein R¹⁴ and R¹⁵ independently are hydrogen, C₁-C₆alkyl orphenyl which is unsubstituted or substituted by halogen. In anotherembodiment the present invention provides a compound of formula Iwherein R⁹ is —NR¹⁴R¹⁵, wherein R¹⁴ and R¹⁵ independently are hydrogen,C₁-C₆alkyl or phenyl which is substituted by halogen.

In one embodiment the present invention provides a compound of formula Iwherein R¹⁰ is hydrogen, C₁-C₆alkyl, C₁-C₆alkyl which is substituted byhydroxy, cyano, C₃-C₆cycloalkyl, COOH or COO—C₁-C₆alkyl; COR wherein Ris C₁-C₆alkyl, halogen-C₁-C₆alkyl, C₁-C₆alkoxy or C₃-C₆cycloalkyl;S(O)₂—C₁-C₆alkyl or C₃-C₆cycloalkyl. In another embodiment the presentinvention provides a compound of formula I wherein R¹⁰ is hydrogen,unsubstituted C₁-C₆alkyl, C₁-C₆alkyl which is substituted by cyano; CORwherein R is C₁-C₆alkyl; or C₃-C₆cycloalkyl. In still another embodimentthe present invention provides a compound of formula I wherein R¹⁰ isunsubstituted C₁-C₆alkyl.

In one embodiment the present invention provides a compound of formula Iwherein R¹¹ is hydrogen or C₁-C₆alkyl. In another embodiment the presentinvention provides a compound of formula I wherein R¹¹ is hydrogen.

In one embodiment the present invention provides a compound of formula Iwherein R¹⁰ and R¹¹ together are C₁-C₆alkylene which is unsubstituted orsubstituted by hydroxy.

In one embodiment the present invention provides a compound of formula Iwherein E is CR²⁰ and -A-B-D- is —CR¹⁷—CR¹⁸—CR¹⁹—, —N—CR¹⁸—CR¹⁹—,—CR¹⁷—N—CR¹⁹—, —CR¹⁷—CR¹⁸—N—, —N—CR¹⁸—N—, —N—N—CR¹⁹—, —N—O—, —NR²¹—N—,—S—N—, —S—CH— or —CH—S—, wherein R¹⁷, R¹⁸ and R²⁰ independently arehydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy or C₂-C₆alkenyl, and R¹⁹ ishydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy, C₂-C₆alkenyl or phenyl. Inanother embodiment the present invention provides a compound of formulaI wherein E is CR²⁰ and -A-B-D- is —CR¹⁷—CR¹⁸—CR¹⁹—, —N—CR¹⁸—CR¹⁹—,—CR¹⁷—N—CR¹⁹—, —CR¹⁷—CR¹⁸—N—, —N—CR¹⁸—N—, —N—N—CR¹⁹—, —N—O—, —NR²¹—N—,—S—N— or —S—CH—, wherein R¹⁷ is hydrogen, halogen or C₁-C₆alkyl; R¹⁸ ishydrogen; R¹⁹ is hydrogen, halogen, C₁-C₆alkyl, halogen-C₁-C₆alkyl,C₁-C₆alkoxy, C₂-C₆alkenyl or phenyl; R²⁰ is hydrogen, halogen orC₁-C₆alkyl; and R²¹ is C₁-C₆alkyl.

In still another embodiment the present invention provides a compound offormula I wherein E is CR²⁰ and -A-B-D- is —CR¹⁷—CR¹⁸—CR¹⁹—,—N—CR¹⁸—CR¹⁹—, —CR¹⁷—N—CR¹⁹—, —N—CR¹⁸—N—, —N—N—CR¹⁹—, —S—N— or —S—CH—,wherein R¹⁷ is hydrogen or halogen; R¹⁸ is hydrogen; R¹⁹ is hydrogen,halogen, C₁-C₆alkyl, halogen-C₁-C₆alkyl or C₂-C₆alkenyl; and R²⁰ ishydrogen or halogen.

In one embodiment the present invention provides a compound of formula Iwherein E is N and -A-B-D- is —CR¹⁷—CR¹⁸—CR¹⁹—, —N—CR¹⁸—CR¹⁹—,—CR¹⁷—N—CR¹⁹—, —N—O—, —S—N—, —S—CH—, —CH—CH— or —CH—S—, wherein R¹⁷, R¹⁸and R²⁰ independently are hydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy orC₂-C₆alkenyl, and R¹⁹ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy,C₂-C₆alkenyl or phenyl. In another embodiment the present inventionprovides a compound of formula I wherein E is N and -A-B-D- is—CR¹⁷—CR¹⁸—CR¹⁹—, —N—CR¹⁸—CR¹⁹—, —CR¹⁷—N—CR¹⁹— or —S—N—, wherein R¹⁷ ishydrogen or halogen; R¹⁸ is hydrogen; and R¹⁹ is hydrogen, halogen orC₁-C₆alkyl.

In still another embodiment the present invention provides a compound offormula I wherein E is N and -A-B-D- is —CR¹⁷—CR¹⁸—CR¹⁹—, —N—CR¹⁸—CR¹⁹—or —CR¹⁷—N—CR¹⁹—, wherein R¹⁷ is hydrogen or halogen; R¹⁸ is hydrogen;and R¹⁹ is hydrogen, halogen or C₁-C₆alkyl.

In one embodiment the present invention provides a compound of formula Iwherein E is S and -A-B-D- is —CH—CH—.

In one embodiment the present invention provides a compound of formula Iwherein n is 1. In one embodiment the present invention provides acompound of formula I wherein n is 3.

In addition to the foregoing the present invention also provides aprocess for the production of a compound of formula I

whereinR¹, R², R⁴ and R⁵ are independently hydrogen, C₁-C₆alkyl, C₁-C₆alkoxy orhalogen;R³ is C₁-C₆alkyl, halogen-C₁-C₆alkyl, C₃-C₆cycloalkyl, Si(C₁-C₆alkyl)₃,—OR¹², wherein R¹² is C₁-C₆alkyl, halogen-C₁-C₆alkyl, C₃-C₆cycloalkyl,phenyl, benzyl or S(O)₂—C₁-C₆alkyl, or pentafluorosulphuranyl; orR² and R³ taken together with the carbon atoms they are attached to forma 5- or 6-membered carbocyclic ring or a 5- or 6-membered heterocyclicring containing one or two heteroatoms selected from N, O or S;R⁶ is hydrogen or C₁-C₆alkyl;R⁷ and R⁸ are independently hydrogen, C₁-C₆alkyl, hydroxy or halogen;R⁹ is hydrogen, C₁-C₆alkyl, C₂-C₆alkenyl, halogen-C₁-C₆alkyl,heterocyclyl, heteroaryl, phenyl, naphthyl, —OR¹³, wherein R¹³ isC₁-C₆alkyl or phenyl, —NR¹⁴R¹⁵, wherein R¹⁴ and R¹⁵ independently arehydrogen, C₁-C₆alkyl or phenyl, or —C(O)—OR¹⁶, wherein R¹⁶ is hydrogenor C₁-C₆alkyl;R¹⁰ and R¹¹ are independently hydrogen, halogen, C₁-C₆alkyl, COR whereinR is C₁-C₆alkyl, C₁-C₆alkoxy or C₃-C₆cycloalkyl, S(O)₂—C₁-C₆alkyl,C₃-C₆cycloalkyl, or phenyl; or together are C₁-C₆alkylene;A is CR¹⁷ or N, wherein R¹⁷ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy or C₂-C₆alkenyl;B is CR¹⁸ or N, wherein R¹⁸ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy or C₂-C₆alkenyl;D is CR¹⁹ or N, wherein R¹⁹ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy, C₂-C₆alkenyl or phenyl;E is CR²⁰ or N, wherein R²⁰ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy or C₂-C₆alkenyl; orE is CR²⁰ and -A-B-D- is —N—O—, —NR²¹—N—, —S—N—, —S—CH— or —CH—S—,wherein R²¹ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy orC₂-C₆alkenyl; or

-   -   E is N and -A-B-D- is —N—O—, —S—N—, —S—CH—, —CH—CH— or —CH—S—;        or        E is S and -A-B-D- is —CH—CH—; and        n is 1, 2 or 3;        which process comprises        reacting an acid derivative, a compound of formula II

whereinR³³ is hydrogen, Li, Na, K or C₁-C₆alkyl; andR¹⁰, R¹¹, A, B, D and E have the above meanings;with a secondary amine derivative, a compound of formula III

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and n have the abovemeanings.

If compounds of formula II are used in this process wherein R³³ ishydrogen or Li, Na or K (acids), standard peptide coupling reagents canbe applied to activate the acid prior to the coupling reaction.Typically, the acid derivative of formula II (R³³ is hydrogen, Li, Na,K) is mixed with a coupling reagent such as EDC or EDC.HCl, DCC, HBTU orTBTU in an inert solvent such as N,N-dimethylformamide,dimethylacetamide (DMA) or dichloromethane (DCM) together with theappropriate secondary amine derivative III. Optionally a base (e.g.N,N-diisopropylethyl amine, triethylamine, N-methyl morpholine) and/or1-hydroxybenzotriazole (HOBT) can be added. The reaction mixture isstirred for 1 to 24 h at a temperature of about −30° C. to about 70° C.(e.g. ambient temperature).

Alternatively, esters of formula II (R³³ is C₁-C₆alkyl, e.g. CH₃ orC₂H₅) may be used in the coupling process. In that case, the aminederivative III is treated with trimethylaluminum in an inert solventsuch as DCM or toluene at ambient temperature prior to the addition ofthe ester derivative II.

In another embodiment the present invention provides a process for theproduction of a compound of formula I wherein

R¹, R², R⁴ and R⁵ are independently hydrogen, C₁-C₆alkyl, C₁-C₆alkoxy orhalogen;

R³ is C₁-C₆alkyl, halogen-C₁-C₆alkyl, C₃-C₆cycloalkyl, Si(C₁-C₆alkyl)₃,—OR¹², wherein R¹² is C₁-C₆alkyl, halogen-C₁-C₆alkyl, C₃-C₆cycloalkyl,phenyl, benzyl or S(O)₂—C₁-C₆alkyl, or pentafluorosulphuranyl; or

R² and R³ taken together with the carbon atoms they are attached to forma 5- or 6-membered carbocyclic ring or a 5- or 6-membered heterocyclicring containing one or two heteroatoms selected from N, O or S;

R⁶ is hydrogen or C₁-C₆alkyl;

R⁷ and R⁸ are independently hydrogen, C₁-C₆alkyl, hydroxy or halogen;

R⁹ is hydrogen, C₁-C₆alkyl, C₂-C₆alkenyl, halogen-C₁-C₆alkyl,heterocyclyl, heteroaryl, phenyl, naphthyl, —OR¹³, wherein R¹³ isC₁-C₆alkyl or phenyl, —NR¹⁴R¹⁵, wherein R¹⁴ and R¹⁵ independently arehydrogen, C₁-C₆alkyl or phenyl, or —C(O)—OR¹⁶, wherein R¹⁶ is hydrogenor C₁-C₆alkyl;R¹⁰ is hydrogen, halogen, C₁-C₆alkyl, COR wherein R is C₁-C₆alkyl,C₁-C₆alkoxy or C₃-C₆cycloalkyl, S(O)₂—C₁-C₆alkyl, C₃-C₆cycloalkyl, orphenyl;R¹¹ is hydrogen;A is CR¹⁷ or N, wherein R¹⁷ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy or C₂-C₆alkenyl;B is CR¹⁸ or N, wherein R¹⁸ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy or C₂-C₆alkenyl;D is CR¹⁹ or N, wherein R¹⁹ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy, C₂-C₆alkenyl or phenyl;E is CR²⁰ or N, wherein R²⁰ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy or C₂-C₆alkenyl; orE is CR²⁰ and -A-B-D- is —N—O—, —NR²¹—N—, —S—N—, —S—CH— or —CH—S—,wherein R²¹ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy orC₂-C₆alkenyl; orE is N and -A-B-D- is —N—O—, —S—N—, —S—CH—, —CH—CH— or —CH—S—; orE is S and -A-B-D- is —CH—CH—; andn is 1, 2 or 3;which process comprisesreacting a compound of formula IV

whereinR¹⁰, A, B, D and E have the above meanings;with a secondary amine derivative, a compound of formula III wherein R¹,R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and n have the above meanings.

A compound of formula IV and a formula III compound are mixed togetherin an inert solvent such as DMF or toluene and the reaction mixture isheated (e.g. to reflux) for 1 to 24 h. Formula IV compounds arecommercially available or can be synthesized according to literatureprocedures or as described in the example section.

In another embodiment the present invention also provides a process forthe production of a compound of formula I wherein

R¹, R², R⁴ and R⁵ are independently hydrogen, C₁-C₆alkyl, C₁-C₆alkoxy orhalogen;

R³ is C₁-C₆alkyl, halogen-C₁-C₆alkyl, C₃-C₆cycloalkyl, Si(C₁-C₆alkyl)₃,—OR¹², wherein R¹² is C₁-C₆alkyl, halogen-C₁-C₆alkyl, C₃-C₆cycloalkyl,phenyl, benzyl or S(O)₂—C₁-C₆alkyl, or pentafluorosulphuranyl; or

R² and R³ taken together with the carbon atoms they are attached to forma 5- or 6-membered carbocyclic ring or a 5- or 6-membered heterocyclicring containing one or two heteroatoms selected from N, O or S;

R⁶ is hydrogen or C₁-C₆alkyl;

R⁷ and R⁸ are independently hydrogen, C₁-C₆alkyl, hydroxy or halogen;

R⁹ is hydrogen, C₁-C₆alkyl, C₂-C₆alkenyl, halogen-C₁-C₆alkyl,heterocyclyl, heteroaryl, phenyl, naphthyl, —OR¹³, wherein R¹³ isC₁-C₆alkyl or phenyl, —NR¹⁴R¹⁵, wherein R¹⁴ and R¹⁵ independently arehydrogen, C₁-C₆alkyl or phenyl, or —C(O)—OR¹⁶, wherein R¹⁶ is hydrogenor C₁-C₆alkyl;R¹⁰ and R¹¹ are independently hydrogen, halogen, C₁-C₆alkyl, COR whereinR is C₁-C₆alkyl, C₁-C₆alkoxy or C₃-C₆cycloalkyl, S(O)₂—C₁-C₆alkyl,C₃-C₆cycloalkyl, or phenyl; or together are C₁-C₆alkylene;E is CR²⁰ and -A-B-D- is —N—CR¹⁸—N—;R¹⁸ and R²⁰ independently are hydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxyor C₂-C₆alkenyl; andn is 1, 2 or 3;which process comprisesreacting a compound of formula V

whereinR³⁴ is halogen, e.g. Cl or F;R³⁵ is hydrogen, Li, Na or K;E is CR²⁰ and -A-B-D- is —N—CR¹⁸—N—; wherein R¹⁸ and R²⁰ independentlyare hydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy or C₂-C₆alkenyl;with a compound of formula III wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸,R⁹ and n have the above meanings,and treating the resulting compound of formula VI

with an amine derivative HNR¹⁰R¹¹.

The reaction may be performed in an inert solvent such as THF, dioxane,water or mixtures thereof at elevated temperatures using conventional ore.g. microwave heating.

Compounds of formula I wherein R¹⁰ and R¹¹ are hydrogen (Ic) can betransformed into compounds of formula I wherein R¹⁰ is C₁-C₆alkyl, CORwherein R is C₁-C₆alkyl, C₁-C₆alkoxy or C₃-C₆cycloalkyl,S(O)₂—C₁-C₆alkyl, C₃-C₆cycloalkyl, or phenyl; and R¹¹ is hydrogen,either by reductive alkylation, by acylation or sulfonylation dependingon the nature of the substituent R¹⁰ that is introduced. Thesealkylation, acylation or sulfonylation reactions can be performed usingstandard conditions described in the literature.

Conversion of formula I compounds wherein R¹⁰ is hydrogen and R¹¹ istrifluoroacetyl, into derivatives of formula I wherein R¹⁰ isC₁-C₆alkyl, can be accomplished in two steps, by reacting a compound offormula I wherein R¹¹ is trifluoroacetyl and R¹⁰ is hydrogen with analkylating agent R¹⁰—X (wherein R¹⁰ is C₁-C₆alkyl and X is halogen, e.g.Cl, Br, I) in the presence of a base such as sodium hydride in an inertsolvent such as DMF or DMA (optionally DMPU can be added) to givecompounds of formula I wherein R¹¹ is trifluoroacetyl and R¹⁰ isC₁-C₆alkyl, followed by cleavage of the trifluoroacetamide group using abase such as sodium hydroxide or potassium hydroxide in a solvent suchas methanol or ethanol at temperatures between 0° C. and 100° C.

In another embodiment the present invention provides a process for theproduction of a compound of formula I wherein

R¹, R², R⁴ and R⁵ are independently hydrogen, C₁-C₆alkyl, C₁-C₆alkoxy orhalogen;

R³ is —OR¹², wherein R¹² is C₁-C₆alkyl, C₃-C₆cycloalkyl, phenyl, benzylor S(O)₂—C₁-C₆alkyl;

R⁶ is hydrogen or C₁-C₆alkyl;

R⁷ and R⁸ are independently hydrogen, C₁-C₆alkyl, hydroxy or halogen;

R⁹ is hydrogen, C₁-C₆alkyl, C₂-C₆alkenyl, halogen-C₁-C₆alkyl,heterocyclyl, heteroaryl, phenyl, naphthyl, —OR¹³, wherein R¹³ isC₁-C₆alkyl or phenyl, —NR¹⁴R¹⁵, wherein R¹⁴ and R¹⁵ independently arehydrogen, C₁-C₆alkyl or phenyl, or —C(O)—OR¹⁶, wherein R¹⁶ is hydrogenor C₁-C₆alkyl;R¹⁰ is hydrogen, halogen, C₁-C₆alkyl, COR wherein R is C₁-C₆alkyl,C₁-C₆alkoxy or C₃-C₆cycloalkyl, S(O)₂—C₁-C₆alkyl, C₃-C₆cycloalkyl, orphenyl;R¹¹ is hydrogen;A is CR¹⁷ or N, wherein R¹⁷ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy or C₂-C₆alkenyl;B is CR¹⁸ or N, wherein R¹⁸ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy or C₂-C₆alkenyl;D is CR¹⁹ or N, wherein R¹⁹ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy, C₂-C₆alkenyl or phenyl;E is CR²⁰ or N, wherein R²⁰ is hydrogen, halogen, C₁-C₆alkyl,C₁-C₆alkoxy or C₂-C₆alkenyl; orE is CR²⁰ and -A-B-D- is —N—O—, —NR²¹—N—, —S—N—, —S—CH— or —CH—S—,wherein R²¹ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy orC₂-C₆alkenyl; orE is N and -A-B-D- is —N—O—, —S—N—, —S—CH—, —CH—CH— or —CH—S—; orE is S and -A-B-D- is —CH—CH—; andn is 1, 2 or 3;which process comprises cleavage of the benzylic ether bond in acompound of formula I wherein R³ is benzyloxy (e.g. with H₂, Pd/C inethyl acetate) and reacting the resulting compound with an alkylatingagent R¹²—X (with X=Cl, Br, I) in the presence of a base such aspotassium carbonate in an inert solvent such as DMF or DMA at atemperature between 0° C. and 100° C.

Acid derivatives of formula II are commercially available or can beprepared as described in the example section.

Secondary amines of the general formula III can be synthesized bystandard methods. They may be synthesized as outlined below.

Compounds of formula III

wherein R⁶ is hydrogen may be prepared by reductive amination of abenzaldehyde, a compound of formula VIII

with an amine, a compound of formula IX

The above reaction may take place in the presence of a suitable reducingagent, e.g. sodium borohydrate.

Alternatively, compounds of formula III wherein R⁶ is hydrogen may beprepared by reacting a compound of formula X

with a compound of formula IXand reducing the resulting amide, compound of formula XI

Compounds of formula VIII and IX are commercially available or may besynthesized using standard methods as e.g. described in the examplesection.

Alternatively, compounds of formula III wherein R⁶ is hydrogen may beprepared by reacting a compound of formula XII

with a compound of formula XIII

and reducing the resulting amide, a compound of formula XIV

Whereas amide derivatives of formula XI are available by the coupling ofbenzoic acid derivatives X with amines IX, amides of formula XIV can besynthesized by coupling benzylic amines XII with acids XIII. These amidecouplings can be accomplished using standard coupling reagents andconditions (as described above). The necessary starting amines and acidsare commercially available or are synthesized using standard conditionsas e.g. described in the example section.

Alternatively, compounds of formula III wherein R⁶ is C₁-C₆alkyl may beprepared by reacting a compound of formula XV

with an alkyllithium reagent R^(r)Li, wherein R^(r) is C₁-C₆ alkyl, e.g.with methyllithium, in the presence of a Lewis acid such as borontrifluoride ethyl etherate.Imines XV are accessible from aldehydes VIII and amines IX by standardmethods

In the examples the following abbreviations are used: RT: roomtemperature; DMF: N,N-dimethylformamide; DCM: dichloromethane.

In general, the nomenclature used in this Application is based onAUTONOM™ v.4.0, a Beilstein Institute computerized system for thegeneration of IUPAC systematic nomenclature.

Preparation of Starting Compounds

Aldehydes (Acids/Nitriles): (Compounds of Formula VIII and X)

EXAMPLE S1-A Preparation of 4-cyclopropyl benzaldehyde

To a solution of 1-bromo-4-cyclopropylbenzene [synthesized in analogy toa procedure described in J. Org. Chem. 1976, 41, 2262-2266] (1.58 g,8.04 mmol) in THF at −78° C. was added n-BuLi (5.08 ml, 1.6M solution inhexane, 8.11 mmol) and the reaction mixture was stirred at −78° C. for10 min. DMF (1.25 ml, 16.08 mmol) was then added and the reactionmixture was stirred at −78° C. for 15 min. The reaction mixture was thenwarmed to 0° C. slowly (over 2 h) and stirred at 0° C. for 1 h. Thereaction was quenched with sat. NH₄Cl_((aq)) solution and the aqueousphase was extracted with ether. The organic layer was washed with brine,dried (MgSO₄), filtered and concentrated in vacuo to give a residuewhich was purified by flash column chromatography (1:9diethylether/pentane) to give 4-cyclopropyl benzaldehyde (1.10 g, 94%)as a colourless oil. ^(1H) NMR (CDCl₃, 300 MHz): δ 9.94 (s, 1H), 7.76(d, J=8.5 Hz, 2H), 7.19 (d, J=8.5 Hz, 2H), 1.97 (m, 1H), 1.13-1.06 (m,2H), 0.84-0.78 (m, 2H).

EXAMPLE S2-A Preparation of 4-cyclobutyl benzaldehyde a) Preparation of1-(4-bromophenyl)-cyclobutanol

To a solution of 1,4-dibromobenzene (1.00 g, 4.24 mmol) at −78° C. inether (20 ml) was added n-BuLi (2.65 ml, 1.6 M solution in hexane, 4.24mmol) and the reaction mixture was stirred at −78° C. for 30 min.Cyclobutanone (348 μl, 4.66 mmol) was then added and the reactionmixture was stirred at −78° C. for 15 min. The reaction mixture was thenslowly (over 2 h) warmed to 0° C. and stirred for a further 1 h. Waterwas added followed by sat. NH₄Cl and the reaction mixture was extractedwith ether. The organic layer was washed with brine, dried (MgSO₄),filtered and concentrated in vacuo to give a residue which was purifiedby flash column chromatography (1:4 ether/pentane) to give1-(4-bromophenyl)-cyclobutanol (330 mg, 34%) as a colourless oil. ^(1H)NMR (CDCl₃, 300 MHz): δ 7.50 (d, J=8.5 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H),2.57-2.48 (m, 2H), 2.41-2.31 (m, 2H), 2.02 (m, 1H), 1.69 (m, 1H).

b) Preparation of bromo-4-cyclobutyl-benzene

To a solution of 1.37 g of 1-(4-bromophenyl)-cyclobutanol (6 mmol) in 15ml DCM were added 1.15 ml of triethylsilane (7.2 mmol) and the mixturewas cooled to −78° C. Then 1.15 ml of boron trifluoride diethyl etheratecomplex were added and the reaction mixture was warmed to −40° C. andstirred for 8 h. The reaction was then quenched by addition of 10%aqueous KHCO₃ and the mixture was extracted three times with DCM. Thecombined extracts were washed with brine, dried with magnesium sulfateand concentrated. The remaining residue was purified by columnchromatography (silica gel; cyclohexane) to give 0.84 g (66%) of1-bromo-4-cyclobutyl-benzene as a colorless liquid. ^(1H) NMR (CDCl₃,300 MHz): δ 1.85 (m, 1H), 1.92-2.18 (m, 3H), 2.33 (m, 2H), 3.49 (quint,J=8.5 Hz, 1H), 7.08 (d, J=8.5 Hz, 2H), 7.40 (d, J=8.5 Hz, 2H).

c) Preparation of 4-cyclobutyl-benzaldehyde

The title compound was synthesized in analogy to 4-cyclopropylbenzaldehyde (described in example S1-A) using 830 mg of1-bromo-4-cyclobutyl-benzene (3.93 mmol), 2.7 ml of a 1.6 molar solutionof n-BuLi in hexane (4.32 mmol) and 605 μl of DMF (7.86 mmol). Theisolated residue was purified by flash column chromatography (5:95EtOAc/cyclohexane) to give 422 mg of 4-cyclobutyl-benzaldehyde (67%) asa colourless liquid. ^(1H) NMR (CDCl₃, 300 MHz): δ 1.89 (m, 1H),1.97-2.26 (m, 3H), 2.40 (m, 2H), 3.63 (quint, J=8.5 Hz, 1H), 7.36 (d,J=8.0 Hz, 2H), 7.81 (d, J=8.0 Hz, 2H), 9.97 (s, 1H).

EXAMPLE S3-A Preparation of 4-cyclopentyl benzaldehyde a) Preparation of1-(4-bromo-phenyl)-cyclopentanol

The title compound was synthesized in analogy to1-(4-bromo-phenyl)-cyclobutanol (described in example S2-A) using 3 g of1,4-dibromobenzene (12.7 mmol), 7.95 ml of a 1.6 molar solution ofn-BuLi in hexane (12.7 mmol) and 1.24 ml of cyclopentanone (14.0 mmol).The isolated residue was purified by flash column chromatography (1:4diethyl ether/pentane) to give 1.2 g of 1-(4-bromo-phenyl)-cyclopentanol(39%) as a colourless liquid.

b) Preparation of 1-bromo-4-cyclopent-1-enyl-benzene

To a solution of 2.62 g of 1-(4-bromo-phenyl)-cyclopentanol (10.9 mmol)in 50 ml toluene were added 124 mg of toluene-4-sulfonic acid (1 mmol)and the mixture was heated to reflux for 4 h. After the reaction mixturewas allowed to cool to RT it was washed with sat. NaHCO₃-solution andbrine, dried (MgSO₄), filtered and concentrated in vacuo to give 2.12 gof 1-bromo-4-cyclopent-1-enyl-benzene (88%) as an off-white solid.

c) Preparation of 1-bromo-4-cyclopentyl-benzene

A mixture of 1.04 g of 1-bromo-4-cyclopent-1-enyl-benzene (4.7 mmol) and100 mg of PtO₂ in 25 ml toluene was stirred under an atmosphere ofhydrogen at RT for 6 h. The reaction mixture was then filtered and thefiltrate was evaporated to dryness to give 1.0 g of1-bromo-4-cyclopentyl-benzene (95%) as a yellow liquid.

d) Preparation of 4-cyclopentyl-benzaldehyde

The title compound was synthesized in analogy to 4-cyclopropylbenzaldehyde (described in example S1-A) using 2.07 g of1-bromo-4-cyclopentyl-benzene (9.2 mmol), 6.32 ml of a 1.6 molarsolution of n-BuLi in hexane (10.11 mmol) and 1.422 ml of DMF (18.4mmol). 4-Cyclopentyl-benzaldehyde was isolated by flash columnchromatography (5:95 EtOAc/c-hexane) as a colorless liquid (1146 mg,72%). ^(1H) NMR (CDCl₃, 300 MHz): δ 1.53-1.91 (m, 6H), 2.11 (m, 2H),3.07 (quint, J=8.5 Hz, 1H), 7.40 (d, J=8 Hz, 2H), 7.80 (d, J=8 Hz, 2H),9.97 (s, 1H).

EXAMPLE S4-A Preparation of 4-(1-methoxy-cyclobutyl)-benzaldehyde a)Preparation of 1-bromo-4-(1-methoxycyclobutyl)-benzene

To a suspension of NaH (24 mg, ˜55% dispersion in oil, 0.53 mmol) in DMF(2 ml) at 0° C. was added a solution of 1-(4-bromophenyl)-cyclobutanol(100 mg, 0.44 mmol, described in example S2-A) in DMF (2 ml). Themixture was stirred at 0° C. for 30 min and then methyl iodide (41 μl,0.66 mmol) was added. The reaction mixture was then warmed up to RT andstirring was continued overnight. The mixture was quenched with waterand extracted with ether. The organic phase was washed with water andbrine, dried (MgSO₄), filtered, and concentrated in vacuo to give aresidue which was purified by flash column chromatography (1:9ether/pentane) to give 1-bromo-4-(1-methoxycyclobutyl)-benzene (79 mg,75%) as a colourless oil. ^(1H)NMR (CDCl₃, 300 MHz): δ 7.50 (d, J=8.5Hz, 2H), 7.30 (d, J=8.5 Hz, 2H), 2.92 (s, 3H), 2.38-2.33 (m, 4H), 1.94(m, 1H), 1.67 (m, 1H).

b) Preparation of 4-(1-methoxycyclobutyl)-benzaldehyde

The title compound was synthesized in analogy to 4-cyclopropylbenzaldehyde (described in example S1-A) using1-bromo-4-(1-methoxycyclobutyl)-benzene (140 mg, 0.58 mmol), n-BuLi (363μl, 1.6M solution in hexane, 0.58 mmol) and DMF (90 μl, 1.16 mmol). Theisolated residue was purified by flash column chromatography (1:9ether/pentane) to give 4-(1-methoxycyclobutyl)-benzaldehyde (76 mg, 69%)as a colourless oil. ^(1H) NMR (CDCl₃, 300 MHz): δ 10.03 (s, 1H), 7.91(d, J=8.5 Hz, 2H), 7.61 (d, J=8.5 Hz, 2H), 2.96 (s, 3H), 2.45-2.39 (m,4H), 1.99 (m, 1H), 1.73 (m, 1H).

EXAMPLE S5-A Preparation of 4-(1-fluoro-cyclobutyl)-benzaldehyde a)Preparation of 1-bromo-4-(1-fluoro-cyclobutyl)-benzene

To a solution of 5.66 g of 1-(4-bromophenyl)-cyclobutanol (24.92 mmol,described in example S2-A) in 70 ml DCM were added 4.23 g of(diethylamino)sulfur trifluoride (95%, 24.92 mmol) at 0° C. The reactionmixture was stirred at 0° C. for 35 min, then sat. NaHCO₃-solution wasadded and the resulting mixture was extracted with DCM. The combinedorganic extracts were washed with brine, dried (MgSO₄), filtered, andconcentrated in vacuo to give a residue which was purified by flashcolumn chromatography (100% pentane) to give1-bromo-4-(1-fluoro-cyclobutyl)-benzene (3.66 g, 64%) as a colourlessliquid.

b) Preparation of 4-(1-fluoro-cyclobutyl)-benzaldehyde

The title compound was synthesized in analogy to 4-cyclopropylbenzaldehyde (described in example S1-A) using 1.64 g of1-bromo-4-(1-fluoro-cyclobutyl)-benzene (7.16 mmol), 4.92 ml of a 1.6molar solution of n-BuLi in hexane (7.87 mmol) and 1.1 ml of DMF (14.32mmol). 4-(1-Fluoro-cyclobutyl)-benzaldehyde was isolated crude as alight yellow liquid (1.23 g, 96%). ^(1H) NMR (CDCl₃, 300 MHz): δ 1.84(m, 1H), 2.15 (m, 1H), 2.49-2.81 (m, 5H), 7.63 (d, J=8 Hz, 2H), 7.92 (d,J=8 Hz, 2H), 10.03 (s, 1H).

EXAMPLE S6-A Preparation of 4-(1-methoxycyclopropyl)-benzaldehydePreparation of 1-bromo-4-(1-methoxycyclopropyl)-benzene

Trimethyl orthoformate (2.75 ml, 25.12 mmol) was added to4-bromoacetophenone (5.00 g, 25.12 mmol) followed by p-toluenesulfonicacid (239 mg, 1.26 mmol). The reaction mixture was stirred at RT for 30h. The methyl formate and methanol formed in the reaction were distilledoff slowly for at least 4 h at 85° C. until no further methanol wasbeing formed. The reaction mixture was cooled to RT and a few drops oftriethylamine were added. The crude residue was then purified by flashcolumn chromatography (5% EtOAc, 1% Et₃N in cyclohexane) to give amixture of 1-bromo-4-(1-methoxyvinyl)-benzene and1-bromo-4-(1,1-dimethoxyethyl)-benzene in a 1:1 mixture. The productswere not separated and reacted in the next step as a mixture.

To a solution of 2,4,6-trichlorophenol (1.90 g, 9.64 mmol) in methylenechloride (70 ml) at −40° C. was added diethyl zinc (9.64 ml, 1M solutionin hexane, 9.64 mmol). The mixture was stirred at −40° C. for 20 min andthen CH₂I₂ (778 μl, 9.64 mmol) was added. After stirring for anadditional 20 min, 1-bromo-4-(1-methoxyvinyl)-benzene (1.37 g, 6.43mmol) was added. The reaction mixture was slowly warmed to RT andstirring was continued for 16 h. Pentane was added and the mixture waswashed with 1M HCl, sat. NaHCO₃, sat. Na₂SO₃ and brine. The organiclayer was dried (MgSO₄), filtered, concentrated in vacuo to give a cruderesidue which was purified by flash column chromatography (2% ethylacetate in cyclohexane-10% ethyl acetate in cyclohexane) to give1-bromo-4-(1-methoxycyclopropyl)-benzene (880 mg, 60%) as a yellow oil.^(1H) NMR (CDCl₃, 300 MHz): δ 7.46 (d, J=8.5 Hz, 2H), 7.18 (d, J=8.5 Hz,2H), 3.21 (s, 3H), 1.21-1.17 (m, 2H), 0.95-0.91 (m, 2H).

b) Preparation of 4-(1-methoxycyclopropyl)-benzaldehyde

The title compound was synthesized in analogy to 4-cyclopropylbenzaldehyde (described in example S1-A) using1-bromo-4-(1-methoxycyclopropyl)-benzene (250 mg, 1.10 mmol), n-BuLi(722 μl, 1.6M solution in hexane, 1.16 mmol) and DMF (171 μl, 2.20mmol). The isolated residue was purified by flash column chromatography(1:9 ether/pentane) to give 4-(1-methoxycyclopropyl)-benzaldehyde (90mg, 58%) as a colourless oil. ^(1H) NMR (CDCl₃, 300 MHz): δ 10.0 (s,1H), 7.79 (d, J=8.5 Hz, 2H), 7.37 (d, J=8.5 Hz, 2H), 3.29 (s, 3H),1.35-1.30 (m, 2H), 1.09-1.05 (m, 2H).

EXAMPLE S7-A Preparation of4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzaldehyde

A solution of 3.5 g of 4-(heptafluoroisopropyl)-toluene (13.4 mmol) in100 ml tetrachloromethane was heated to reflux. Then 2.63 g ofN-bromosuccinimide (14.8 mmol) and 326 mg of dibenzoyl peroxide (1.34mmol) were added in small portions. After 5 h the mixture was cooled to0° C., filtered and the solvent was evaporated. The remaining residuewas dissolved in 15 ml ethanol and was added to a suspension that hadbeen prepared by addition of 2-nitropropane (1.4 ml, 15.5 mmol) to asolution of 340 mg sodium (14.8 mmol) in ethanol. This mixture wasstirred for 3 days. Then it was filtered, the solvent was removed andthe remaining residue was dissolved in EtOAc and washed with 1 N sodiumhydroxide solution, 1 N HCl solution, saturated NaHCO₃ solution and withbrine. The EtOAc layer was then dried with magnesium sulfate, filteredand concentrated. Purification of the residue (silica gel;c-hexane/EtOAc 10:1) gave 1.1 g (30%) of4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzaldehyde as a lightyellow oil. ^(1H)-NMR (CDCl₃, 300 MHz): δ 7.82 (d, J=8 Hz, 2H), 8.03 (d,J=8 Hz, 2H), 10.11 (s, 1H).

EXAMPLE S8-A Preparation of 2-chloro-4-cyclopropyl-benzaldehyde a)Preparation of 4-bromo-2-chloro-benzoic acid methyl ester

3.0 g of 4-bromo-2-chloro-benzoic acid (12.74 mmol) were dissolved in 60ml methanol and treated with 0.6 ml of concentrated HCl. After 17 h atreflux the reaction mixture was concentrated in vacuo, diluted with DCMand washed with a saturated aqueous NaHCO₃ solution and brine, driedwith magnesium sulfate, filtered and concentrated in vacuo leading to2.7 g (85%) of 4-bromo-2-chloro-benzoic acid methyl ester as a lightyellow oil. MS (+cEI): 250.0 (M).

b) Preparation of 2-chloro-4-cyclopropyl-benzoic acid methyl ester

2.1 g of crude 4-bromo-2-chloro-benzoic acid methyl ester (8.42 mmol)were dissolved in 38 ml toluene and treated with 0.94 g ofcyclopropylboronic acid (10.94 mmol), 6.25 g of potassium phosphate(29.46 mmol), 236 mg of triphenylphosphine (0.84 mmol), 94 mg ofpalladium acetate (0.42 mmol) and 1.9 ml water. The reaction mixture wasstirred 17 h at 100° C. under Argon. After cooling down to RT, thereaction mixture was treated with 80 ml water, extracted with 2×80 mlEtOAc, washed with brine, dried over magnesium sulfate, filtered andconcentrated in vacuo. The remaining residue was purified by silicagelchromatography (100 g silicagel, heptane/AcOEt 95:5) leading to 1.17 gof 2-chloro-4-cyclopropyl-benzoic acid methyl ester (66%) as a yellowoil. MS (+cEI): 210.1 (M).

c) Preparation of 2-chloro-4-cyclopropyl-benzaldehyde

To a solution of 7.01 ml Red-Al 13.5 M (24.54 mmol) in toluene was addedat 0° C. a solution of 3.0 ml 1-methylpiperazine (26.89 mmol) in 16 mltoluene over 30 min. The resulting solution was then added dropwise over40 min to 1.1 g of 2-chloro-4-cyclopropyl-benzoic acid methyl ester (5.2mmol) in 32 ml toluene between −5° C. and 0° C. After stirring for 30min at this temperature, the reaction mixture was cooled to −10° C. andtreated dropwise with 30 ml water. The mixture was then filtered,diluted with ethylacetate, washed with 1N—HCl, brine, dried overmagnesium sulfate, filtered again and concentrated in vacuo, leading to0.98 g of 2-chloro-4-cyclopropyl-benzaldehyde as a brown oil (100%). MS(+cEI): 180.1 (M).

EXAMPLE S9-A Preparation of 4-pentafluoroethyl-benzonitrile

A mixture of 4-iodobenzonitrile (10.0 g, 43.7 mmol), sodiumpentafluoroproprionate (15.4 g, 82.9 mmol), and copper(I) iodide (16.6g, 87.3 mmol), DMF (160 mL), and toluene (60 mL) was heated at 160° C.for 16 h, allowing most of the toluene to distil off. After cooling,ethyl acetate (200 mL) was added, and the mixture was filtered throughdiatomaceous earth, and the filtrate was partitioned between ethylacetate/heptane and water. The organic layer was washed with brine,dried (MgSO₄), and evaporated. Chromatography (SiO₂, heptane-ethylacetate gradient) afforded the title compound (5.05 g 52%). Yellow oil,MS (EI) 221.1 (M⁺).

EXAMPLE S10-A Preparation of 4-pentafluoroethyl-benzoic acid

A mixture of 4-pentafluoroethyl-benzonitrile (2.98 g, 13.5 mmol) andpotassium hydroxide (3.03 g, 54.0 mmol) in water (40 mL) and ethanol (20mL) was heated at reflux for 16 h. After cooling, the solution waspartitioned between 1 M aq. hydrochloric acid solution and ethylacetate. The organic layer was washed with brine, dried (MgSO₄), andevaporated. Chromatography (SiO₂, heptane-ethyl acetate gradient)produced the title compound (2.76 g, 85%). White solid, MS (ISP) 238.9(M−H)⁻.

EXAMPLE S11-A Preparation of 4-(1-fluoro-cyclopropyl)benzoic acid a)Preparation of 1-(2,2-dichloro-1-fluoro-cyclopropyl)-4-methyl-benzene

50% aq. sodium hydroxide solution (4.4 mL, 54 mmol) was added dropwiseat 0° C. to a solution of 1-(1-fluoro-vinyl)-4-methyl-benzene (J. Med.Chem. 2004, 47, 5860; 1.84 g, 13.5 mmol) and benzyltriethylammoniumchloride (123 mg, 0.54 mmol) in chloroform (20 mL), then after 30 minthe ice bath was removed and stirring continued over 16 h. Ice water wasadded, the organic layer was subsequently washed with 0.1 M aq.hydrochloric acid solution, 5% aq. sodium hydrogencarbonate solution andbrine, dried (MgSO₄), and evaporated. Chromatography (SiO₂, heptane)afforded the title compound (2.54 g, 86%). Light yellow liquid, MS (EI)218.0 (M⁺).

b) Preparation of 1-(1-fluoro-cyclopropyl)-4-methyl-benzene

A solution of 1-(2,2-dichloro-1-fluoro-cyclopropyl)-4-methyl-benzene(1.18 g, 5.39 mmol) in THF (10 mL) was added at 0° C. to a suspension oflithium aluminum hydride (1.64 g, 43.1 mmol) in THF. The reactionmixture was stirred for 16 h at RT, then another portion of lithiumaluminum hydride (613 mg, 16.1 mmol) was added, then after 3 h, 1 M aq.potassium sodium tartrate solution, methanol and ethyl acetate wereadded. The organic layer was washed with brine, dried (MgSO₄), andevaporated. Chromatography (SiO₂, heptane) afforded the title compound(702 mg, 87%). Colourless liquid, MS (EI) 150.1 (M⁺).

c) Preparation of 4-(1-fluoro-cyclopropyl)benzoic acid

Oxygen was slowly bubbled at 100° C. through a solution of1-(1-fluoro-cyclopropyl)-4-methyl-benzene (470 mg, 3.13 mmol),cobalt(II)acetate tetrahydrate (117 mg, 0.46 mmol), and acetaldehyde(0.18 mL, 3.1 mmol) in acetic acid (30 mL) over 16 h. After cooling, thereaction mixture was evaporated and the residue triturated in water. Theprecipitate was collected by filtration to produce the title compound(257 mg, 46%). Light green solid, MS (EI) 180.1 (M⁺).

EXAMPLE S12-A Preparation 4-cyclopropyl-3-fluoro-benzaldehyde

The title compound was prepared in analogy to2-chloro-4-cyclopropyl-benzaldehyde described in example S8-A. MS (ISP):165.2 (M+H)⁺

EXAMPLE S13-A Preparation 4-cyclopropyl-2-fluoro-benzaldehyde

The title compound was prepared in analogy to2-chloro-4-cyclopropyl-benzaldehyde described in example S8-A. MS (ISP):165.2 (M+H)⁺

EXAMPLE S14-A Preparation of 4-trimethylsilanyl-benzaldehyde

Bromo-4-(trimethylsilyl)benzene (1.15 g, 5 mmol) was dissolved in THF(30 ml) and cooled to −78° C. Under argon a 1.6 M solution of n-butyllithium in hexane (3.13 ml, 5 mmol) was added dropwise keeping thetemperature below −70° C. The clear colorless solution was stirred at−78° C. for 15 min and DMF (1.156 ml, 15 mmol) was added quickly. Thereaction temperature increased to −68° C. The reaction was stirred foradditional 15 min at −78° C., quenched with 1N aqueous hydrogen chloridesolution and extracted twice with diethyl ether. The combined organiclayers were washed twice with water and once with saturated aqueoussodium chloride solution, dried over sodium sulfate, filtered and thesolvent was evaporated to afford the product as a colorless oil (920 mg,100%). The product was pure enough to be used directly in the next step.MS (ISP) 179.2 (M+H⁺). ^(1H)NMR (CDCl₃, 300 MHz): δ 10.02 (s, 1H) 7.84(d, 2H), 7.69 (d, 2H), 0.31 (s, 9H).

Primary Amines: (Compounds of Formula IX)

EXAMPLE S1-B Preparation of2-(3-fluoro-4-trifluoromethyl-phenyl)-ethylamine hydrochloride

3 g of (3-fluoro-4-trifluoromethyl-phenyl)-acetonitrile (14.5 mmol) weredissolved in 23 ml THF and cooled down to 0° C. under nitrogen. 77 ml ofa 1M borane-THF complex solution in THF were then added dropwise over 35min by keeping the temperature between 0-2° C. After addition thereaction mixture was stirred at RT for additional 45 min, and thenrefluxed for 21 h. The reaction mixture was then cooled down to 0° C.and treated between 2 and 5° C. with 17 ml methanol over a period of 30min. After 1 h refluxing the reaction mixture was concentrated, theremaining residue was dissolved in DCM and the mixture was extractedtwice with 1N aqueous HCl. The combined aqueous phases were then treatedwith concentrated NaOH to adjust the pH to 12, and then extracted twicewith DCM. The combined organic phases were then washed with water, driedover magnesium sulfate, filtered and concentrated in vacuo leading to2.1 g yellow oily residue. This was dissolved in 50 ml diethylether,treated with 5 ml 2.6N HCl in diethylether, stirred at RT for additional15 min, evaporated to dryness and dried under vacuo, leading to 2.34 gof the title compound as a white solid (66%). MS (ISP) 208.2 (M+H)⁺.

EXAMPLE S2-B Preparation of2-(4-chloro-3-trifluoromethyl-phenyl)-ethylamine hydrochloride a)Preparation of (4-chloro-3-trifluoromethyl-phenyl)-acetonitrile

3.94 g of 4-bromomethyl-1-chloro-2-trifluoromethyl-benzene (14.4 mmol)and 1.06 g sodium cyanide (21.6 mmol) were suspended in 12 ml DMSO underargon and stirring and heated to 50° C. for 1 h. The reaction mixturewas then poured on water/ice and extracted four times with DCM. Thecombined organic phases were washed with water, dried with magnesiumsulfate, filtered and concentrated in vacuo, leading to 3.188 g of(4-chloro-3-trifluoromethyl-phenyl)-acetonitrile as a dark red oil,which was directly used in the next step.

b) Preparation of 2-(4-chloro-3-trifluoromethyl-phenyl)-ethylaminehydrochloride

The title compound was synthesized in analogy to2-(3-fluoro-4-trifluoromethyl-phenyl)-ethylamine hydrochloride(described in example S1-B) from 3.188 g of crude(4-chloro-3-trifluoromethyl-phenyl)-acetonitrile (14.5 mmol) and 76 mlof a 1M borane-THF complex solution in THF (76 mmol). The product wasobtained as a white solid (1.52 g, 40%). MS (ISP) 224.1 (M+H)⁺.

EXAMPLE S3-B Preparation of (R)-2-(4-chloro-phenyl)-2-hydroxy-ethylaminehydrochloride

1.9 g of (R (4-chloro-phenyl)-hydroxy-acetonitrile (11 mmol) weredissolved in 18 ml THF under a nitrogen atmosphere and the solution wascooled to 0° C. 58 ml of a 1M borane-THF complex solution in THF werethen added dropwise, keeping the temperature between 0-2° C. Aftercompletion of the addition the reaction mixture was stirred at RT foradditional 45 min and then refluxed for 16 h. The reaction mixture wasthen cooled down to 0° C. and 13 ml of methanol were added over a periodof 35 min keeping the temperature of the mixture between 2 and 5° C.After refluxing the reaction mixture for 1 h it was concentrated, theremaining residue was dissolved in DCM and the mixture was extractedtwice with 1N aqueous HCl. The combined aqueous phases are then treatedwith concentrated NaOH to adjust the pH to 12, and then extracted twicewith DCM. The combined organic phases were then washed with water, driedwith magnesium sulfate, filtered and concentrated in vacuo leading to acolorless solid which was dissolved in 100 ml diethylether, treated with4 ml 2.6N HCl in diethyl ether. After 1 h at RT the precipitate wasfiltered off and dried under high vacuum, leading to 1.24 g white solid(54%). MS (ISP) 172.1 (M+H)⁺.

EXAMPLE S4-B Preparation of 2-(4-chloro-3-fluoro-phenyl)-ethylamine(S4-B1) a) Preparation of 1-chloro-2-fluoro-4-(2-nitro-vinyl)-benzene

4-Chloro-3-fluorobenzaldehyde (13 g, 82 mmol) and ammonium acetate (14.6g, 189 mmol) were dissolved in acetic acid (150 ml) and nitromethane(12.6 ml, 234 mmol) was added. The solution was heated to reflux for 1.5h. After cooling to RT water (120 ml) was added. A solid precipitated.The reaction was extracted three times with methylene chloride. Thecombined organic layers were washed with water and sat. aq. NaClsolution, dried over magnesium sulfate, filtered and the solvent wasremoved in vacuo. The residue was purified by flash columnchromatography (Ethyl acetate/cyclohexane:1/4). The crude product wassuspended in heptane, filtered and dried to yield1-chloro-2-fluoro-4-(2-nitro-vinyl)-benzene (10.9 g, 66%) as a lightyellow solid. ^(1H) NMR (CDCl₃, 300 MHz): δ 7.29 (d, J=7.8 Hz, 1H), 7.33(d, J=9.3 Hz, 1H), 7.50 (t, J=7.5H, 1H), 7.54 (d, J=13.6 Hz, 1H), 7.92(d, J=13.6 Hz, 1H).

b) Preparation of 2-(4-chloro-3-fluoro-phenyl)-ethylamine

Lithium borohydride (2.16 g, 99 mmol) was suspended in THF (50 ml).Trimethylchlorosilane (21.6 g, 198 mmol) was added dropwise. A solutionof 1-chloro-2-fluoro-4-(2-nitro-vinyl)-benzene (5.0 g, 24.8 mmol) in THF(20 ml) was added dropwise. Strong gas evolution and foam formation wasobserved. The white suspension was stirred at RT for 3 days. CarefullyMeOH (80 ml) was added. The solvents were removed in vacuo and theresidue was purified by flash column chromatography (CH₂Cl₂/MeOH+5% aq.NH₄OH 4:1) to yield 2-(4-chloro-3-fluoro-phenyl)-ethylamine (3.1 g, 73%)as a white solid. MS (ISP) 174.1 (M+H)⁺. ^(1H)NMR (DMSO-d₆, 300 MHz):δ2.92 (t, J=4.8 Hz, 2H), 3.02 (t, J=6.3 Hz, 2H), 7.15 (dd, J=6.0 and 1.2Hz, 1H), 7.38 (dd, J=1.2 and 7.8 Hz), 7.53 (t, J=6.3 Hz, 1H), 7.93 (br,2H).

MS (ISP) Example Name * (M + M)⁺ S4-B22-(3-Difluoromethoxy-phenyl)-ethylamine hydrochloride S1-B 188.3 S4-B32-(3-Chloro-4-fluoro-phenyl)-ethylamine hydrochloride S1-B 174.1 S4-B42-(3-Trifluoromethoxy-phenyl)-ethylamine hydrochloride S1-B 206.2 S4-B52-(2-Fluoro-3-trifluoromethyl-phenyl)-ethylamine S1-B 208.1hydrochloride S4-B6 2-(3-Chloro-2-fluoro-phenyl)-ethylaminehydrochloride S1-B 174.2 *: Prepared in analogy to exampleSecondary Amines: (Compounds of Formula III)

EXAMPLE S1-C Preparation of(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amine

0.38 ml of 4-tert-butylbenzaldehyde (2.25 mmol) and 0.227 ml2-(3,4-dichloro-phenyl)-ethylamine (1.5 mmol) were dissolved in 4.5 mlmethanol at RT, and after stirring for 30 min at RT, were refluxed for 2h. After cooling down to RT, 85 mg (2.25 mmol) sodium borohydride wereadded and after stirring for 5 min at RT, the reaction mixture was thenrefluxed for 2 h. After cooling down to RT, the reaction mixture wastreated with 4 drops 1 N HCl and concentrated in vacuo. The residue wasdiluted with water/EtOAc. After separation of the organic phase, theaqueous phase was extracted with EtOAc and the combined organic phaseswere washed with brine, dried with magnesium sulfate, filtered off andconcentrated in vacuo. The residue was purified by column chromatography(40 g silica gel; EtOAc/heptane 1:2) to give 515 mg colorless viscousoil (97%). MS (ISP) 336.2 (M+H)⁺.

EXAMPLE S2-C Preparation of(4-tert-butyl-benzyl)-[2-(4-fluoro-3-trifluoromethyl-phenyl)-ethyl]-amine

0.62 ml of 4-tert-butylbenzaldehyde (3.69 mmol), 600 mg of2-(4-fluoro-3-trifluoromethyl-phenyl)-ethylamine hydrochloride (2.46mmol) and 340 mg of potassium carbonate (2.46 mmol) were suspended in 7ml methanol at RT, and after stirring for 30 min at RT, were refluxedfor 2 h. After cooling down to RT, 140 mg (3.69 mmol) of sodiumborohydride were added and after stirring for 5 min at RT, the reactionmixture was then refluxed for 3 h. After cooling down to RT, thereaction mixture was treated with 0.5 ml 1 N HCl and concentrated invacuo. The residue was diluted with water/EtOAc. After separation of theorganic phase, the aqueous phase was extracted with EtOAc and thecombined organic phases were washed with brine, dried with magnesiumsulfate, filtered off and concentrated in vacuo. The residue waspurified by column chromatography (40 g silica gel; EtOAc/heptane 1:4then 1:2) to give 784 mg light yellow oil (90%). MS (ISP) 354.3 (M+H)⁺.

EXAMPLE S3-C Preparation of[2-(4-chlorophenyl)-ethyl]-(4-cyclopropylbenzyl)-amine

A mixture of 4-cyclopropyl benzaldehyde (204 mg, 1.40 mmol),2-(4-chlorophenyl)-ethyl-amine (217 mg, 1.40 mmol) and molecular sieves(500 mg, 4 Å) in diethyl ether (4 ml) was stirred at RT overnight. Themixture was filtered through celite® and concentrated in vacuo to givethe corresponding imine which was dissolved in methanol. Sodiumborohydride (79 mg, 2.09 mmol) was added and the reaction mixture wasstirred at RT for 4 h. The reaction mixture was then quenched with 0.1NNaOH_((aq)) and the mixture was diluted with EtOAc and washed withbrine. The organic phase was dried (MgSO₄), filtered and concentrated invacuo to give the desired[2-(4-chlorophenyl)-ethyl]-(4-cyclopropylbenzyl)-amine (317 mg, 79%)without further purification as a colourless oil. MS (ISP) 285.9 (M+H)⁺.

EXAMPLE S4-C Preparation of(4-tert-butyl-benzyl)-[2-(2-chloro-pyridin-4-yl)-ethyl]-amine a)Preparation of 2-chloro-4-trimethylsilanylethynyl-pyridine

A mixture of 2.5 g of 4-bromo-2-chloropyridine (12.6 mmol), 2.2 ml of(trimethylsilyl)acetylene (15.1 mmol), 153 mg of copper(I)iodide (0.79mmol) and 287 mg of bis(triphenylphosphine)palladium(II)chloride (0.41mmol) in triethylamine (15 ml) was stirred at RT for 1 h. Thetriethylamine was then removed in vacuo, water was added and the mixturewas extracted with diethylether. The combined organic extracts were thenwashed with water and brine, dried (Na₂SO₄), filtered and concentratedin vacuo to give a residue which was purified by column chromatography(heptane/EtOAc 100:0 to 98:2) to give2-chloro-4-trimethylsilanylethynyl-pyridine (2.394 g, 91%) as a lightyellow liquid. MS (ISP) 210.1 (M+H)⁺.

b) Preparation of 2-chloro-4-ethynyl-pyridine

To a solution of 2.389 g of 2-chloro-4-trimethylsilanylethynyl-pyridine(11.39 mmol) in THF (90 ml) were added 11.39 ml of a 1M TBAF solution inTHF at −78° C. and the reaction mixture was stirred for 45 min at 0° C.Then saturated NH₄Cl solution was added and the THF was removed underreduced pressure. The aqueous mixture was extracted with diethyletherand the combined organic extracts were washed with water and brine,dried (Na₂SO₄), filtered and concentrated in vacuo. The remainingresidue was purified by column chromatography (pentane/diethylether100:0 to 4:1) to give 2-chloro-4-ethynyl-pyridine (1.427 g, 91%) as anoff-white solid. ¹H-NMR (CDCl₃, 300 MHz): δ 3.36 (s, 1H), 7.27 (dd, J=5and 1 Hz, 2H), 7.40 (br s, 1H), 8.37 (d, J=8 Hz, 2H).

c) Preparation of(4-tert-butyl-benzyl)-[2-(2-chloro-pyridin-4-yl)-ethyl]-amine

A mixture of 1.386 g of 2-chloro-4-ethynyl-pyridine (10.07 mmol), 2.65ml of 4-tert-butyl-benzylamine (15.11 mmol), 0.58 ml of acetic acid(10.07 mmol) and 666 mg of sodium cyanoborohydride (95% purity, 10.07mmol) in ethanol (12 ml) were heated to 105° C. in a sealed tube for 2d. The reaction mixture was allowed to cool to RT, diluted with 3N NaOHsolution and extracted with DCM. The combined organic extracts werewashed with saturated NaHCO₃ solution and brine, dried (Na₂SO₄),filtered and concentrated in vacuo. After column chromatography(heptane/EtOAc 100:0 to 0:100) 1.688 g (55%) of the title compound wereisolated as a brown liquid. MS (ISP) 303.2 (M+H)⁺.

EXAMPLE S5-C Preparation of(4-tert-butyl-benzyl)-(2,2-difluoro-2-phenyl-ethyl)-amine a) Preparationof N-(4-tert-butyl-benzyl)-2,2-difluoro-2-phenyl-acetamide

(Diethylamino)sulfur trifluoride (1.71 g, 11.2 mmol) was added at RT toneat ethyl benzoyl-formate (1.00 g, 5.61 mmol), then after 16 h excessreagent was destroyed by addition of ice. The reaction mixture waspartitioned between ethyl acetate and water, the organic layer washedwith sat. aq. sodium hydrogencarbonate solution, dried (MgSO₄), andevaporated. To the residue was added 1 M aq. sodium hydroxide solution(7 mL), the slurry was stirred at RT for 24 h, acidified with 1 M aq.hydrochloric acid solution (10 mL), and extracted with tert-butyl methylether. The organic layer was washed with brine, dried (MgSO₄), andevaporated. The residue was dissolved in DMF (60 mL), then afteraddition of 4-tert-butylbenzylamine (957 mg, 6.17 mmol),4-methylmorpholine (1.62 g, 16.8 mmol) and HBTU (3.03 g, 25.3 mmol) thesolution was stirred at RT for 16 h. The reaction mixture was thenpartitioned between water and ethyl acetate, the organic layer waswashed with brine, dried (MgSO₄), and evaporated. Chromatography (SiO₂,heptane-ethyl acetate gradient) afforded the title compound (1.16 g,69%). White solid, MS (ISP) 318.1 (M+H)⁺.

b) Preparation of(4-tert-butyl-benzyl)-(2,2-difluoro-2-phenyl-ethyl)-amine

Borane-tetrahydrofuran complex solution (1 M in THF, 1.89 mL, 1.89 mmol)was added at 0° C. to a solution ofN-(4-tert-butyl-benzyl)-2,2-difluoro-2-phenyl-acetamide (200 mg, 0.63mmol) in THF (3.2 mL), then the ice bath was removed and the solutionheated to reflux over 16 h. After cooling, the reaction was quenched bycareful addition of 1 M aq. hydrochloric acid solution. The reactionmixture was neutralized with aq. sodium hydroxide solution and extractedwith DCM. The organic layer was washed with brine, dried (MgSO₄),evaporated, and chromatographed (SiO₂, heptane-ethyl acetate gradient).The fractions containing the product were concentrated, the residuedissolved in 5% ethanolic sulfuric acid solution (2 mL). This solutionwas heated at reflux for 2 h, neutralized with 2 M aq. sodium hydroxidesolution, and extracted with ethyl acetate. The organic layer was washedwith brine, dried (MgSO₄), and evaporated to produce the title compound(74 mg, 39%). Light yellow oil, MS (ISP) 304.3 (M+H)⁺.

EXAMPLE S6-C Preparation of[2-(4-chloro-phenyl)-ethyl]-(4-pentafluoroethyl-benzyl)-amine

Diisobutylaluminum hydride solution (1 M in hexane, 5.0 mL, 5.0 mmol)was added at 0° C. to a solution of 4-pentafluoroethyl-benzonitrile(1.00 g, 4.52 mmol) in DCM (5 mL), then after 2 h another portion ofdiisobutylaluminum hydride solution (5 mL) was added and the reactionstirred at RT for 16 h, then carefully poured onto 50% aq. sulfuric acidsolution (4 mL). Water (45 mL) was added, and the mixture is extractedthree times with DCM. The organic layer was subsequently washed withbrine and 1 M potassium sodium tartrate solution, dried (MgSO₄), andevaporated. Chromatography (SiO₂, heptane-ethyl acetate gradient)afforded crude 4-pentafluoroethyl-benzaldehyde (390 mg) as a yellowliquid, which was added at RT to a solution of2-(4-chlorophenyl)ethylamine (269 mg, 1.73 mmol) in methanol (2 mL),then after 18 h sodium borohydride (65 mg, 1.73 mmol) was added at 0° C.After 1 h the reaction mixture was partitioned between ether and water,the organic layer was washed with brine, dried (MgSO₄), and evaporated.Chromatography (SiO₂, heptane-ethyl acetate gradient) afforded the titlecompound (431 mg, 26%). Light yellow oil, MS (ISP) 364.1 (M+H)⁺.

EXAMPLE S7-C Preparation of(4-pentafluoroethyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-aminea) Preparation of 4-pentafluoroethyl-benzylamine

A solution of 4-pentafluoroethyl-benzonitrile (1.00 g, 4.52 mmol) indiethyl ether (6.5 mL) was added at RT to a suspension of lithiumaluminum hydride (172 mg, 4.52 mmol), then after 30 min the reaction wasterminated by careful addition of 1 M aq. potassium sodium tartratesolution. The reaction mixture was extracted three times with tert-butylmethyl ether, the organic layer was extracted with 1 M aq. hydrochloricacid solution, the water layer was basified with 50% aq. sodiumhydroxide solution and extracted with tert-butyl methyl ether. Theorganic layer was washed with brine, dried (MgSO₄), and evaporated.Chromatography (SiO₂, DCM/methanol/NH₄OH 95:5:0.1) afforded the titlecompound (489 mg, 48%). Yellow-liquid, MS (ISP) 226.1 (M+H)⁺.

b) Preparation ofN-(4-pentafluoroethyl-benzyl)-2-(3-trifluoromethyl-phenyl)-acetamide

A solution of 4-pentafluoroethyl-benzylamine (485 mg, 2.16 mmol),3-(trifluoromethyl)-phenylacetic acid (484 mg, 2.37 mmol),4-methylmorpholine (654 mg, 6.46 mmol), and HBTU (1.23 g, 3.23 mmol) inDMF (30 mL) was stirred at RT for 16 h, then the reaction mixture waspartitioned between water and ethyl acetate. The organic layer waswashed with brine, dried (MgSO₄), and evaporated. Chromatography (SiO₂,heptane-ethyl acetate gradient) afforded the title compound (692 mg,78%). Light yellow solid, MS (ISP) 412.2 (M+H)⁺.

c) Preparation of(4-pentafluoroethyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amine

Borane-tetrahydrofuran complex solution (1 M in THF, 2.43 mL, 2.43 mmol)was added at 0° C. to a solution ofN-(4-pentafluoroethyl-benzyl)-2-(3-trifluoromethyl-phenyl)-acetamide(200 mg, 0.486 mmol) in THF (3.2 mL), and the homogeneous solution washeated at reflux over 90 min. After cooling, excess reagent wasdestroyed by careful addition of methanol at 0° C. Volatile material wasremoved by distillation, then the residue was dissolved in 5% ethanolicsulfuric acid solution (2 mL). The solution was refluxed for 2 h, thenpartitioned between 2 M aq. sodium hydroxide solution and ethyl acetate.The organic layer was washed with brine, dried (MgSO₄), and evaporated.Chromatography (SiO₂, heptane-ethyl acetate gradient) afforded the titlecompound (161 mg, 83%). Colourless oil, MS (ISP) 398.2 (M+H)⁺.

EXAMPLE S8-C Preparation of[2-(3-methoxy-phenyl)-ethyl]-(4-pentafluoroethyl-benzyl)-aminePreparation ofN-[2-(3-methoxy-phenyl)-ethyl]-4-pentafluoroethyl-benzamide

A solution of 4-pentafluoroethyl-benzoic acid (500 mg, 2.08 mmol),2-(3-methoxyphenyl)-ethylamine (361 mg, 2.29 mmol), 4-methylmorpholine(632 mg, 6.24 mmol), and HBTU (1.19 g, 3.12 mmol) in DMF (38 mL) wasstirred at RT for 16 h, then the reaction mixture was partitionedbetween water and ethyl acetate. The organic layer was washed withbrine, dried (MgSO₄), and evaporated. Chromatography (SiO₂,heptane-ethyl acetate gradient) afforded the title compound (746 mg,96%). Light yellow solid, MS (ISP) 374.2 (M+H)⁺.

b) Preparation of[2-(3-methoxy-phenyl)-ethyl]-(4-pentafluoroethyl-benzyl)-amine

Borane-tetrahydrofuran complex solution (1 M in THF, 9.9 mL, 9.9 mmol)was added at 0° C. to a solution ofN-[2-(3-methoxy-phenyl)-ethyl]-4-pentafluoroethyl-benzamide (740 mg,1.98 mmol) in THF (12 mL), and the homogeneous solution was heated atreflux over 3 h. After cooling, excess reagent was destroyed by carefuladdition of methanol at 0° C. Volatile material was removed bydistillation, then the residue was dissolved in 5% ethanolic sulfuricacid solution (8 mL). The solution was refluxed for 2 h, thenpartitioned between 2 M aq. sodium hydroxide solution and ethyl acetate.The organic layer was washed with brine, dried (MgSO₄), and evaporated.Chromatography (SiO₂, DCM/methanol/NH₄OH 95:5:0.1) afforded the titlecompound (600 mg, 84%). Colourless oil, MS (ISP) 360.1 (M+H)⁺.

EXAMPLE S9-C Preparation of(4-tert-butylbenzyl)-[2-(4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethyl]-amineand(4-tert-butylbenzyl)-[2-(4-chloro-3-methyl-5-trifluoromethyl-pyrazol-1-yl)-ethyl]-amine(S9-C1) a) Preparation of 2-(4-tert-butylbenzylamino)-ethanol

The title compound was synthesized in analogy to example S3-C using4-tert-butylbenzaldehyde (1000 mg, 6.17 mmol), ethanolamine (371 μl,6.17 mmol) and sodium borohydride (350 mg, 9.25 mmol). The desiredproduct (1190 mg, 93%) was isolated without further purification as acolourless oil. MS (ISP) 208.3 (M+H)⁺.

b) Preparation of 3-(4-tert-butylbenzyl)-[1,2,3]oxathiazolidine2,2-dioxide

To a solution of 2-(4-tert-butylbenzylamino)-ethanol (1190 mg, 5.74mmol) and triethylamine (3200 μl, 22.96 mmol) in DCM (15 ml) at −15° C.was added a solution of thionylchloride (544 μl, 7.46 mmol) in DCM (4ml) over 10 min. The reaction mixture was stirred at −10° C. for 30 min,filtered and the filtrate was concentrated in vacuo. The residue waspurified by flash column chromatography to give the desired compound(790 mg, 54%) as a white solid. To a mixture of3-(4-tert-butylbenzyl)-[1,2,3]oxathiazolidine 2-oxide (790 mg, 3.12mmol) in DCM (20 ml), acetonitrile (8 ml) and water (8 ml), at 0° C. wasadded NaIO4 (867 mg, 4.05 mmol) followed by RuO₂ (2 mg). The reactionmixture was stirred at 0° C. for 2 h. Water was added and the phaseswere separated and the aqueous phase was extracted with ethyl acetate.The organic layers were combined washed with brine, dried (MgSO₄), andconcentrated in vacuo. The residue was then purified by flash columnchromatography to give the desired product (640 mg, 76%) as an off whitesolid. MS (ISP) 287.0 (M+NH₄)⁺.

c) Preparation of(4-tert-butylbenzyl)-[2-(4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethyl]-amineand(4-tert-butylbenzyl)-[2-(4-chloro-3-methyl-5-trifluoromethyl-pyrazol-1-yl)-ethyl]-amine

To a suspension of NaH (58 mg, 1.11 mmol) in THF (10 ml) at 0° C. wasadded a solution of 4-chloro-5-methyl-3-trifluoromethyl-1H-pyrazole (206mg, 1.11 mmol) in THF (5 ml) drop wise. The reaction mixture was stirredat 0° C. for 30 min and then3-(4-tert-butylbenzyl)-[1,2,3]oxathiazolidine 2,2-dioxide (300 mg, 1.11mmol) was added portion wise. The reaction mixture was warmed to RT andstirred for a further 3 hr after which the reaction mixture was quenchedwith 5 ml 20% (v/v) H₂SO₄. The reaction mixture was warmed to 60° C.overnight and then cooled to RT and poured into water. The aqueous phasewas made basic with 1N NaOH and then extracted with ethyl acetate. Theorganic layers were combined, washed with brine, dried over MgSO₄,filtered and concentrated in vacuo to give a 7:3 mixture of regioisomers(4-tert-butylbenzyl)-[2-(4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethyl]-amine(223 mg, 54%) MS (ISP) 374.3 (M+H)⁺ and(4-tert-butylbenzyl)-[2-(4-chloro-3-methyl-5-trifluoromethyl-pyrazol-1-yl)-ethyl]-amine(110 mg, 26%) MS (ISP) 374.3 (M+H)⁺ respectively which were separated byflash column chromatography.

MS (ISP) Example Name * (M + H)⁺ S9-C2(4-tert-Butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)- S1-C 336.3ethyl]-amine S9-C3 (4-tert-Butyl-benzyl)-phenethyl-amine S1-C 268.3S9-C4 (4-tert-Butyl-benzyl)-[2-(3-fluoro-4-trifluoromethyl- S2-C 354.3phenyl)-ethyl]-amine S9-C5(4-tert-Butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)- S2-C 352.3ethyl]-amine S9-C6(4-Cyclopropyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)- S2-C 336.5ethyl]-amine S9-C7 (4-tert-Butyl-benzyl)-[2-(4-chloro-3-trifluoromethyl-S2-C 370.2 phenyl)-ethyl]-amine S9-C8(4-Cyclopropylbenzyl)-[2-(3-trifluoromethoxyphenyl)- S3-C 320.2ethyl]-amine S9-C9 (4-tert-Butyl-benzyl)-[2-(3-difluoromethoxy-phenyl)-S2-C 334.3 ethyl]-amine S9-C10 Butyl-(4-tert-butyl-benzyl)-amine S1-C220.4 S9-C11 (4-tert-Butyl-benzyl)-[2-(3-chloro-4-fluoro-phenyl)- S2-C320.3 ethyl]-amine S9-C12(4-tert-Butyl-benzyl)-[2-(2-fluoro-3-trifluoromethyl- S2-C 354.3phenyl)-ethyl]-amine S9-C13(4-tert-butyl-benzyl)-[2-(3-chloro-2-fluoro-phenyl)- S2-C 320.3ethyl]-amine S9-C14N′-(4-tert-Butyl-benzyl)-N-(4-chloro-phenyl)-N-methyl- S1-C 368.2ethane-1,2-diamine S9-C15 [4-(1-Methoxycyclopropyl)-benzyl]-[2-(3- S3-C350.4 trifluoromethylphenyl)-ethyl]-amine S9-C16(4-Pentafluoro-sulphuranyl-benzyl)-[2-(3,4-dichloro- S1-C 406.1phenyl)-ethyl]-amine S9-C17[2-(3,4-Dichloro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro- S1-C 448.01-trifluoromethyl-ethyl)-benzyl]-amine S9-C18[4-(1,2,2,2-Tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]- S1-C 448.1[2-(3-trifluoromethyl-phenyl)-ethyl]-amine S9-C19[2-(4-Fluoro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-S1-C 398.1 ethyl)-benzyl]-amine S9-C20[2-(4-Chloro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1- S1-C 414.3trifluoromethyl-ethyl)-benzyl]-amine S9-C21(2-Chloro-4-cyclopropyl-benzyl)-[2-(3-trifluoromethyl- S1-C 354phenyl)-ethyl]-amine S9-C22(4-Cyclopropyl-2-fluoro-benzyl)-[2-(3-trifluoromethyl- S1-C 337.9phenyl)-ethyl]-amine S9-C23(4-Cyclopropyl-3-fluoro-benzyl)-[2-(3-trifluoromethyl- S1-C 338.0phenyl)-ethyl]-amine S9-C24(4-Cyclobutyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]- S1-C 334.4 amineS9-C25 (4-Cyclobutyl-benzyl)-[2-(3-trifluoromethyl-phenyl)- S1-C 334.4ethyl]-amine S9-C26 (4-Cyclobutyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-S1-C 284.4 amine S9-C27[2-(4-Chloro-phenyl)-ethyl]-(4-cyclobutyl-benzyl)- S1-C 300.4 amineS9-C28 (4-Cyclopentyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]- S1-C348.4 amine S9-C29 (4-Cyclopentyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-S1-C 348.4 ethyl]-amine S9-C30(4-Cyclopentyl-benzyl)-[2-(4-fluoro-3-trifluoromethyl- S1-C 366.2phenyl)-ethyl]-amine S9-C31(4-Cyclobutyl-benzyl)-[2-(4-fluoro-3-trifluoromethyl- S1-C 352.2phenyl)-ethyl]-amine S9-C32(4-tert-Butyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amine S1-C 286.2S9-C33 (4-tert-Butyl-benzyl)-[2-(4-chloro-phenyl)-ethyl]-amine S1-C302.3 S9-C34 (4-tert-Butyl-benzyl)-[2-(3-chloro-phenyl)-ethyl]-amineS1-C 302.3 S9-C35 (4-Trifluoromethoxy-benzyl)-[2-(3-trifluoromethyl-S1-C 364 phenyl)-ethyl]-amine S9-C36(4-tert-Butyl-benzyl)-[2-(2-chloro-phenyl)-ethyl]-amine S1-C 302.3S9-C37 [4-(1-Fluoro-cyclobutyl)-benzyl]-[2-(3-trifluoromethyl- S1-C352.4 phenyl)-ethyl]-amine S9-C38[2-(3,4-Dichloro-phenyl)-ethyl]-[4-(1-fluoro- S1-C 352.3cyclobutyl)-benzyl]-amine S9-C39[2-(3,4-Dichloro-phenyl)-ethyl]-[4-(1-methoxy- S1-C 364.3cyclobutyl)-benzyl]-amine S9-C40[(R)-2-(4-Chloro-phenyl)-2-hydroxy-ethyl]-(4-cyclo- S2-C 302.2propyl-benzyl)-amine S9-C41(4-tert-Butyl-benzyl)-[2-(5-chloro-pyridin-2-yl)-ethyl]- S4-C 303.2amine S9-C42 (4-tert-Butyl-benzyl)-[2-(5-trifluoromethyl-pyridin-2- S4-C337.3 yl)-ethyl]-amine S9-C43(4-tert-Butyl-benzyl)-[2-(6-trifluoromethyl-pyridin-2- S4-C 337.3yl)-ethyl]-amine S9-C44(4-tert-Butyl-benzyl)-[2-(4-trifluoromethyl-pyridin-2- S4-C 337.3yl)-ethyl]-amine S9-C45(4-Methyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- S1-C 294.3 amineS9-C46 (4-Ethyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- S1-C 308.3amine S9-C47 (4-Isopropyl-benzyl)-[2-(3-trifluoromethyl-phenyl)- S1-C322.3 ethyl]-amine S9-C48[2-(3,4-Dichloro-phenyl)-ethyl]-(4-isopropyl-benzyl)- S1-C 322.3 amineS9-C49 [2-(4-Chloro-phenyl)-ethyl]-(4-isopropyl-benzyl)-amine S1-C 288.1S9-C50 (4-Isopropyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)- S2-C 338.2ethyl]-amine S9-C51(4-tert-Butyl-benzyl)-(2-naphthalen-2-yl-ethyl)-amine S1-C 318.2 S9-C52(4-tert-Butyl-benzyl)-(2-phenoxy-ethyl)-amine S1-C 284.3 S9-C53N-(4-tert-Butyl-benzyl)-N′-(4-chloro-phenyl)-ethane S1-C 317.21,2-diamine S9-C54 [2-(4-Chloro-phenyl)-ethyl]-[4-(1-methoxy- S1-C 316.0cyclopropyl)-benzyl]-amine S9-C55[4-(1-Methoxy-cyclopropyl)-benzyl]-[2-(3- S2-C 366.0trifluoromethoxy-phenyl)-ethyl]-amine S9-C56(4-Cyclopropyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]- S1-C 270.1 amineS9-C57 [2-(4-Fluoro-phenyl)-ethyl]-(4-trifluoromethoxy- S1-C 314.0benzyl)-amine S9-C58 [2-(4-Chloro-phenyl)-ethyl]-(4-trifluoromethoxy-S1-C 330.2 benzyl)-amine S9-C59(4-tert-Butoxy-benzyl)-[2-(4-chloro-phenyl)-ethyl]- S1-C 318.0 amineS9-C60 (4-tert-Butoxy-benzyl)-[2-(4-fluoro-phenyl)-ethyl]- S1-C 302.3amine S9-C61 (4-tert-Butoxy-benzyl)-[2-(3-trifluoromethyl-phenyl)- S1-C352.2 ethyl]-amine S9-C62(4-tert-Butoxy-benzyl)-[2-(3-trifluoromethoxy-phenyl)- S2-C 368.3ethyl]-amine S9-C63 [2-(4-Chloro-phenyl)-ethyl]-(4-phenoxy-benzyl)-amineS1-C 337.9 S9-C64[2-(4-Chloro-phenyl)-ethyl]-(4-trifluoromethyl-benzyl)- S1-C 313.9 amineS9-C65 (4-Benzyloxy-benzyl)-[2-(3-trifluoromethyl-phenyl)- S1-C 386.3ethyl]-amine S9-C66 [2-(4-Chloro-phenyl)-ethyl]-[4-(1,1,2,2-tetrafluoro-S1-C 362.0 ethoxy)-benzyl]-amine S9-C67(3-Chloro-4-trifluoromethoxy-benzyl)-[2-(4-fluoro- S1-C 348.4phenyl)-ethyl]-amine S9-C68 [2-(3-Trifluoromethyl-phenyl)-ethyl]-(4-S1-C 352.4 trimethylsilanyl-benzyl)-amine S9-C69[2-(4-Chloro-phenyl)-ethyl]-(4-trimethylsilanyl-benzyl)- S1-C 318.1amine S9-C70 [2-(4-Fluoro-phenyl)-ethyl]-(4-trimethylsilanyl-benzyl)-S1-C 302.2 amine S9-C71[2-(3,4-Dichloro-phenyl)-ethyl]-(4-trimethylsilanyl- S1-C 352.2benzyl)-amine S9-C72 [2-(4-Fluoro-phenyl)-ethyl]-(4-pentafluoroethyl-S8-C 348.2 benzyl)-amine S9-C73(4-Pentafluoroethyl-benzyl)-[2-(3-trifluoromethoxy- S8-C 414.3phenyl)-ethyl]-amine S9-C74(4-Pentafluoroethyl-benzyl)-(2-p-tolyl-ethyl)-amine S8-C 344.1 S9-C75[4-(1-Fluoro-cyclopropyl)-benzyl]-[2-(3- S8-C 338.2trifluoromethyl-phenyl)-ethyl]-amine S9-C76[2-(4-Chloro-phenyl)-ethyl]-[4-(1-fluoro-cyclopropyl)- S8-C 304.1benzyl]-amine S9-C77(4-tert-butylbenzyl)-[2-(3-trifluoromethyl-pyrazol-1-yl)- S9-C 326.4ethyl]-amine S9-C78(4-tert-butylbenzyl)-[2-(5-trifluoromethyl-pyrazol-1-yl)- S9-C 326.4ethyl]-amine S9-C79(4-tert-butylbenzyl)-[2-(4-trifluoromethylimidazol-1-yl)- S9-C 326.3ethyl]-amine S9-C80(4-tert-butylbenzyl)-[2-(3-phenylpyrazol-1-yl)-ethyl]- S9-C 334.3 amineS9-C81 (4-tert-butylbenzyl)-[2-(4-chloro-3- S9-C 360.1trifluoromethylpyrazol-1-yl)-ethyl]-amine S9-C82(4-tert-butylbenzyl)-[2-(5-methyl-3- S9-C 340.2trifluoromethylpyrazol-1-yl)-ethyl]-amine S9-C83(4-tert-Butyl-benzyl)-[2-(4-chloro- S1-C 320.33-fluoro-phenyl)-ethyl]-amine *: Prepared in analogy to exampleAcids, Esters, Benzo[d][1,3]oxazine-2,4-diones: (Compounds of formula IIand IV)

EXAMPLE S1-D Preparation of6-chloro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione

To a solution of 1 g of 6-chloro-1H-benzo[d][1,3]oxazine-2,4-dione (5.06mmol) in DMF (20 ml) were carefully added 265 mg of sodium hydride (55%dispersion in oil, 6.07 mmol) at 0° C. and the mixture was stirred at RTfor 30 min. Then 0.47 ml of methyl iodide (7.60 mmol) were added andstirring at RT was continued over night. Water was added and theresulting mixture was extracted with ethyl acetate. The combined organicextracts were washed with brine, dried (MgSO₄), filtered andconcentrated and the remaining residue was purified by crystallizationfrom heptane. This yielded 513 mg of6-chloro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (48%) as anoff-white solid. ^(1H)NMR (DMSO-d₆, 300 MHz): δ 3.45 (s, 3H), 7.47 (d,J=8.9 Hz, 1H), 7.89 (dd, J=8.9 and 2.7 Hz, 1H), 7.95 (d, J=2.7 Hz, 1H).

EXAMPLE S2-D Preparation of 5-chloro-2-methylamino-benzoic acid

A suspension of 3.955 g of6-chloro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (18.69 mmol) in 37ml of 2N KOH was heated to 100° C. for 4 h. The clear solution was thenallowed to cool to RT and the pH was adjusted to 6-7 by addition of 3NHCl. The precipitate formed was filtered off and dried to give 3.31 g(95%) of the title compound as a yellow solid. MS (ISP) 183.9 (M−H)⁻.

EXAMPLE S3-D Preparation of6-chloro-1-ethyl-1H-benzo[d][1,3]oxazine-2,4-dione

The title compound was prepared in analogy to of6-chloro-1-methyl-1H-benzo[d][1,3]-oxazine-2,4-dione described inexample S1-D. ^(1H)NMR (DMSO-d₆, 300 MHz): δ 1.21 (t, J=7.1 Hz, 3H),4.05 (q, J=7.1 Hz, 2H), 7.54 (d, J=9.0 Hz, 1H), 7.88 (dd, J=9.0 and 2.6Hz, 1H), 7.96 (d, J=2.6 Hz, 1H).

EXAMPLE S4-D Preparation of 5-chloro-2-ethylamino-benzoic acid

The title compound was prepared in analogy to5-chloro-2-methylamino-benzoic acid described in example S2-D. ^(1H)NMR(DMSO-d₆, 300 MHz): δ 1.13 (t, J=7.2 Hz, 3H), 3.13 (d, J=7.2 Hz, 2H),6.69 (d, J=8.9 Hz, 1H), 7.32 (dd, J=8.9 and 2.7 Hz, 1H), 7.64 (d, J=2.7Hz, 1H).

EXAMPLE S5-D Preparation of 5-chloro-2-isopropylamino-benzoic acid a)Preparation of 2-amino-5-chlorobenzoic acid methyl ester

To a suspension of 6-chloro-1H-benzo[d][1,3]oxazine-2,4-dione (10 g,50.61 mmol) in methanol (200 ml) was added DMAP (615 mg, 5.03 mmol) andthe reaction mixture was heated to reflux for 3 h. The reaction mixturewas cooled to RT and concentrated in vacuo. The residue was dissolved inEtOAc and washed with 0.1M HCl solution (3×), brine, dried over MgSO₄,filtered and concentrated in vacuo to give the desired product (9.25 g,97%) as a white solid which did not require further purification. ^(1H)NMR (DMSO-d₆, 300 MHz): δ 7.64 (d, J=2.5 Hz, 1H), 7.30 (dd, J=2.5 and9.0 Hz, 1H), 6.82 (d, J=9.0 Hz, 1H), 6.78 (br s, 2H), 3.79 (s, 3H).

b) Preparation of 5-chloro-2-isopropylamino-benzoic acid methyl ester

To a solution of 500 mg of 2-amino-5-chlorobenzoic acid methyl ester(2.69 mmol) were added slowly 380 μl of 2-methoxypropene (4.04 mmol),154 μl of acetic acid (2.69 mmol) and 951 mg of sodiumtriacetoxyborohydride (4.04 mmol). The reaction mixture was stirred atRT for 3.5 d, then 1N NaOH solution was added and the mixture wasextracted with DCM. The combined organic extracts were washed withbrine, dried (MgSO₄), filtered and concentrated in vacuo. The remainingresidue was purified by column chromatography (silica gel; heptane 100%to heptane/EtOAc 9:1) to give 488 mg (80%) of a yellow liquid. MS (ISP)228.1 (M+H)⁺.

c) Preparation of 5-chloro-2-isopropylamino-benzoic acid

To a solution of 480 mg of 5-chloro-2-isopropylamino-benzoic acid methylester in methanol (5 ml) were added 3.16 ml of a 1N NaOH solution andthe mixture was stirred for 4 d at RT. Then the reaction mixture wasconcentrated in vacuo and the remaining residue dissolved in water. Theresulting solution was washed with ethyl acetate and then the pH wasadjusted to 1 with 1N HCl solution and the mixture was extracted withethyl acetate. The combined organic extracts were dried (MgSO₄),filtered and concentrated to give the title compound as an off-whitesolid (429 mg, 95%). NMR (CDCl₃, 300 MHz): δ 1.27 (d, J=6.3 Hz, 6H),3.70 (sept, J=6.3 Hz, 1H), 6.65 (d, J=9.1 Hz, 1H), 7.31 (dd, J=9.1 and2.7 Hz, 1H), 7.92 (d, J=2.7 Hz, 1H).

EXAMPLE S6-D Preparation of 5-chloro-2-methylamino-nicotinic acid

A mixture of 2,5-dichloronicotinic acid (1.76 g, 9.17 mmol), 41% aq.methylamine solution (7 mL), and 1,4-dioxane (6 mL) was heated at 160°C. under microwave irradiation for 20 min. After cooling, volatilematerial was distilled off, and the residue was dissolved in water (30mL) and acidified to pH 3 by addition of 37% aq. hydrochloric acidsolution. The precipitate was collected by filtration and triturated inDCM to produce the title compound (1.60 g, 92%). Off-white solid, MS(ISP): 187.1 (M+H)⁺.

EXAMPLE S7-D Preparation of 6-chloro-3-methylamino-pyridine-2-carboxylicacid

A mixture of 2-chloro-5-fluoropyridine-6-carboxylic acid (2.00 g, 11.4mmol), 41% aq. methylamine solution (8 mL) and 1,4-dioxane (8 mL) washeated at 125° C. under microwave irradiation for 60 min. After cooling,volatile material was distilled off, and the residue was dissolved inwater (20 mL) and acidified to pH 3 by addition of 37% aq. hydrochloricacid solution. The precipitate was collected by filtration to producethe title compound (1.85 g, 87%). Light yellow solid, MS (ISP): 185.1(M−H)⁻.

EXAMPLE S8-D Preparation of6-chloro-3-methylamino-pyridazine-4-carboxylic acid

41% aq. methylaminine solution (2 mL) was added at RT to a solution of3,6-dichloro-pyridazinecarboxylic acid (500 mg, 2.59 mmol) in1,4-dioxane (2 mL). The reaction mixture was stirred at RT for 5 h, thenevaporated to dryness. The residue was dissolved in water (5 mL) andacidified to pH 3 by addition of 37% aq. hydrochloric acid solution. Theprecipitate was collected by filtration to produce the title compound(321 mg, 66%). White solid, MS (EI): 187.1 (M⁺).

EXAMPLE S9-D Preparation of 3-methylamino-pyridazine-4-carboxylic acid

A mixture of 6-chloro-3-methylamino-pyridazine-4-carboxylic acid (60 mg,0.32 mmol), sodium hydroxide (50 mg, 1.3 mmol), palladium (10% onactivated charcoal, 12 mg), and ethanol (3 mL) was hydrogenated atatmospheric pressure for 48 h, then acidified to pH 7 by addition of 37%aq. hydrochloric acid solution. After removal of insoluble material byfiltration, the filtrate was evaporated and dried to give a white solid(76 mg), which contained the title compound and sodium chloride. MS(ISP): 154.1 (M+H)⁺.

EXAMPLE S10-D Preparation of6-methoxy-3-methylamino-pyridazine-4-carboxylic acid

A solution of 6-chloro-3-methylamino-pyridazine-4-carboxylic acid (80mg, 0.43 mmol), sodium methoxide solution (5.4 M in methanol, 1.0 mL,5.4 mmol) in methanol (1 mL) was heated at 170° C. for 20 min. Aftercooling, the solution was evaporated, the residue dissolved in water (2mL) and acidified to pH 3 by addition of 37% aq. hydrochloric acidsolution. The precipitate was collected by filtration to afford thetitle compound (17 mg, 22%). White solid, MS (ISP): 182.1 (M−H)⁻.

EXAMPLE S11-D Preparation of 2-chloro-5-methylamino-isonicotinic acid a)Preparation of5-(tert-butoxycarbonyl-methyl-amino)-2-chloro-isonicotinic acid

n-Butyllithium solution (1.6 M in hexane, 6.78 mL, 10.8 mmol) was addedat −78° C. to a solution of(6-chloro-4-iodo-pyridin-3-yl)-methyl-carbamic acid tert-butyl ester(synthesized according to WO 2005002577; 2.00 g, 5.43 mmol) in THF (40mL). After 15 min the solution was purged with carbon dioxide gas for 15min, then allowed to reach RT. The reaction mixture partitioned betweenhexane and water and the organic layer was extracted with 1% aq. ammoniasolution. The combined aqueous layer was washed with hexane/ethylacetate 1:1, and the pH was set to 4 by addition of 1 M aq. hydrochloricacid solution. The precipitate was collected by filtration and washedwith water, to afford5-(tert-butoxycarbonyl-methyl-amino)-2-chloro-isonicotinic acid (1.28 g,83%). Yellow solid, MS (ISP): 287.1 (M+H)⁺.

b) Preparation of 2-chloro-5-methylamino-isonicotinic acid

5-(tert-Butoxycarbonyl-methyl-amino)-2-chloro-isonicotinic acid (1.04 g,3.63 mmol) was converted into 2-chloro-5-methylamino-isonicotinic acid(625 mg, 92%) by heating at 240° C. in a Kugelrohr apparatus for 10 min.Yellow solid, MS (ISP): 187.1 (M+H)⁺.

EXAMPLE S12-D Preparation of6-chloro-3-methylamino-pyrazine-2-carboxylic acid

A solution of 3,6-dichloro-pyrazine-2-carboxylic acid methyl ester(synthesized according to GB1082060; 210 mg, 1.01 mmol) in methanol (1.1mL) was treated at 0° C. with 1 M sodium hydroxide solution (1.1 mL, 1.1mmol) and stirred for 1 h at 0° C., then partitioned between ethylacetate and 1 M hydrochloric acid solution. The organic layer was washedwith brine, dried (MgSO₄), and evaporated. The residue was dissolved in1,4-dioxane (0.78 mL), treated with 41% aq. methylamine solution, andthe mixture was heated at 50° C. for 16 h, then partitioned betweenethyl acetate and 0.5 M citric acid solution. The organic layer waswashed with brine, dried (MgSO₄), and evaporated. The residue wastriturated in water to produce the title compound (111 mg, 58%). Yellowsolid, MS (ISP): 186.0 (M−H)⁻.

EXAMPLE S13-D Preparation of 5-bromo-2-methylamino-nicotinic acid ethylester

A suspension of 5-bromo-2-methylamino-nicotinic acid (1.00 g, 4.33 mmol)in 15% ethanolic sulfuric acid solution (15 mL) was heated at reflux for16 h, then poured onto ice, basified to pH 10 with 1 M aq. sodiumcarbonate solution and extracted with ethyl acetate. The organic layerwas washed with brine, dried (MgSO₄), and evaporated. Chromatography(SiO₂, heptane-ethyl acetate gradient) afforded the title compound (929mg, 83%). Light brown solid, MS (ISP): 259.2 (M+H)⁺.

EXAMPLE S14-D Preparation of 2-methylamino-5-vinyl-nicotinic acid ethylester

A solution of 5-bromo-2-methylamino-nicotinic acid ethyl ester (100 mg,0.39 mmol), lithium chloride (98 mg, 2.32 mmol), copper(I)chloride (191mg, 1.93 mmol), vinyl tributyl tin (151 mg, 0.46 mmol), andtetrakis(triphenylphosphine)palladium(0) (45 mg, 39 μmol) in methylsulfoxide (3.1 mL) was stirred at 65° C., then after 4 h another portionof vinyl tributyl tin (141 mg, 0.46 mmol) was added, and stirring wascontinued for 18 h. After cooling, the reaction mixture was partitionedbetween sat. aq. ammonium chloride solution and diethyl ether, theorganic layer was washed with water, dried (MgSO₄), and evaporated.Chromatography (SiO₂, heptane-ethyl acetate gradient) afforded the titlecompound (72 mg, 91%). Yellow liquid, MS (ISP): 207.1 (M+H)⁺.

EXAMPLE S15-D Preparation of 2-methylamino-5-phenyl-nicotinic acid ethylester

A mixture of 5-bromo-2-methylamino-nicotinic acid ethyl ester (100 mg,0.39 mmol), potassium carbonate (160 mg, 1.16 mmol),dichloro[1,1′-bis(diphenylphosphine)ferrocene]palladium(II); (28 mg, 39μmol) and phenylboronic acid (146 mg, 1.16 mmol), 1,4-dioxane (0.9 mL),and water (0.11 mL) was heated at reflux for 3 h, then partitionedbetween ethyl acetate and sat. aq. ammonium chloride solution. Theorganic layer was washed with brine, dried (MgSO₄), and evaporated.Chromatography (SiO₂, heptane-ethyl acetate gradient) afforded the titlecompound (44 mg, 44%). Yellow liquid, MS (EI): 256.2 (M⁺).

EXAMPLE S16-D Preparation of 5-ethyl-2-methylamino-nicotinic acid ethylester

A solution of 5-bromo-2-methylamino-nicotinic acid ethyl ester (400 mg,1.54 mmol), diethylzinc solution (1 M in hexane, 3.1 mL, 3.1 mmol), anddichloro[1,1′-bis(diphenylphosphine)ferrocene]palladium(II) (34 mg, 46μmol) in 1,4-dioxane was heated at reflux for 2 h, then partitionedbetween ethyl acetate and sat. aq. ammonium chloride solution. Theorganic layer was washed with brine, dried (MgSO₄), and evaporated.Chromatography (SiO₂, heptane-ethyl acetate gradient) afforded the titlecompound (48 mg, 15%). Colourless liquid, MS (ISP): 209.3 (M+H)⁺.

EXAMPLE S17-D Preparation of2-cyclopropylamino-5-trifluoromethyl-benzoic acid

1 g of 2-fluoro-5-trifluoromethyl-benzoic acid (4.81 mmol) was dissolvedin DCM (10 ml) and 1.03 ml of oxalylchloride (12.01 mmol) and a drop ofDMF were added at RT. The mixture was stirred for 1 h before allvolatile materials were removed in vacuo. The remaining residue wasagain dissolved in DCM (10 ml) and 1.4 ml of ethanol was added. After 1h the reaction mixture was diluted with DCM and then washed with 10%aqueous KHCO₃ solution, water and brine, dried (MgSO₄), filtered andconcentrated. The remaining material was dissolved in DMSO (6 ml), 5.57ml of cyclopropylamine (79.4 mmol) were added and the mixture was heatedto 110° C. over night in a sealed tube. The reaction mixture was thencooled to RT, diluted with ethyl acetate, washed with diluted HCl, 10%aqueous KHCO₃ solution, water and brine, dried (MgSO₄), filtered andconcentrated. Then THF (20 ml), methanol (10 ml) and 8 ml of a 1N LiOHsolution were added and the resulting solution was stirred over night atRT. The organic solvents were then removed in vacuo and the solution wasacidified with 1N HCl and extracted with ethyl acetate. The combinedorganic extracts were dried (MgSO₄), filtered and concentrated. Theremaining solid was triturated with a small amount of chloroform.Filtration gave 391 mg (33%) of the title compound as light browncrystals. ^(1H)NMR (DMSO-d₆, 300 MHz): δ 0.53 (m, 2H), 0.85 (m, 2H),2.56 (m, 1H), 7.24 (d, J=8.9 Hz, 1H), 7.71 (dd, J=8.9 and 2.1 Hz, 1H),8.02 (s, 1H), 8.30 (br s, 1H), 13.21 (br s, 1H).

EXAMPLE S18-D Preparation of 5-chloro-2-cyclopropylamino-benzoic acid

To a solution of 500 mg of 2-amino-5-chloro-benzoic acid (2.91 mmol) inmethanol were added 3 Å molecular sieves, 2.34 ml of[(1-ethoxycyclopropyl)oxy]trimethylsilane (11.66 mmol) and 1.67 ml ofacetic acid and the mixture was stirred for 30 min at RT. Then 916 mg ofsodium cyanoborohydride (14.57 mmol) were added and the reaction mixturewas heated to reflux for 16 h. The reaction mixture was allowed to coolto RT, filtered and the filtrate was concentrated in vacuo. Theremaining solid was dissolved in ethyl acetate and the solution waswashed with 1N HCl and brine, dried (MgSO₄), filtered and concentratedto give 312 mg of the crude title compound that was used in thefollowing step without further purification. ^(1H)NMR (DMSO-d₆, 300MHz): δ 0.46 (m, 2H), 0.79 (m, 2H), 3.44 (m, 1H), 7.10 (d, J=8.9 Hz,1H), 7.44 (d, J=8.9 Hz, 1H), 7.70 (s, 1H), 7.89 (br s, 1H), 13.09 (br s,1H).

EXAMPLE S19-D Preparation of potassium;3-methylamino-thiophene-2-carboxylate a) Preparation of3-(2,2,2-trifluoro-acetylamino)-thiophene-2-carboxylic acid methyl ester

To a solution of 2 g of methyl 3-amino-thiophene-2-carboxylic acidmethyl ester (12.6 mmol) in DCM (20 ml) were slowly added 2.68 ml oftrifluoroacetic acid anhydride (18.9 mmol) and 3.04 ml of pyridine (37.8mmol) at −10° C. The reaction mixture was stirred for 1 h at RT, pouredinto a mixture of ice and 1N HCl and then extracted with DCM. Thecombined organic extracts were washed with brine, dried (Na₂SO₄),filtered and concentrated in vacuo. The remaining residue was purifiedby column chromatography (silica gel; heptane 100% to heptane/EtOAc 9:1)to give 3.019 g (95%) of3-(2,2,2-trifluoro-acetylamino)-thiophene-2-carboxylic acid methyl estera white solid. MS (ISP) 252.1 (M−H)⁻.

b) Preparation of3-[methyl-(2,2,2-trifluoro-acetyl)-amino]-thiophene-2-carboxylic acidmethyl ester

A mixture of 2 g of3-(2,2,2-trifluoro-acetylamino)-thiophene-2-carboxylic acid methyl ester(7.9 mmol), 1.31 g of potassium carbonate (9.48 mmol) and 596 μl ofmethyl iodide (9.48 mmol) in DMF (7.5 ml) was stirred for 2 d. Thereaction mixture was then poured into water and extracted with DCM. Thecombined organic extracts were washed with water and brine, dried(Na₂SO₄), filtered and concentrated in vacuo to give 2.055 g (97%) of3-[methyl-(2,2,2-trifluoro-acetyl)-amino]-thiophene-2-carboxylic acidmethyl ester as a white solid. MS (ISP) 268.1 (M+H)⁺.

c) Preparation of 3-methylamino-thiophene-2-carboxylic acid methyl ester

A solution of 2.05 g of3-[methyl-(2,2,2-trifluoro-acetyl)-amino]-thiophene-2-carboxylic acidmethyl ester (7.67 mmol) in a mixture of methanol (100 ml) and 1N NaOH(15.4 ml) was stirred at RT over night. The methanol was then removed invacuo and the remaining mixture was diluted with water and extractedwith ethyl acetate. The combined organic layers were washed with brine,dried (Na₂SO₄), filtered and concentrated in vacuo to give 1.236 g (94%)of 3-methylamino-thiophene-2-carboxylic acid methyl ester as a lightbrown solid. MS (ISP) 172.2 (M+H)⁺.

d) Preparation of potassium; 3-methylamino-thiophene-2-carboxylate

To a solution of 230 mg of 3-methylamino-thiophene-2-carboxylic acidmethyl ester (1.34 mmol) in methanol (4 ml) was added a solution of 262mg of potassium hydroxide in 322 μl of water and the mixture was heatedto reflux for 1.5 d. The reaction mixture was then concentrated in vacuoand the remaining residue was dried. This gave 399 mg of a light brownsolid containing the crude title compound (contaminated with excess ofpotassium hydroxide) that was used in the following step without furtherpurification. MS (ISP) 156.0 (M−H)⁻.

EXAMPLE S20-D Preparation of lithium5-cyclopropylamino-thiazole-4-carboxylate a) Preparation of5-cyclopropylamino-thiazole-4-carboxylic acid ethyl ester

To a vigorously stirred solution of 311 mg of potassium tert-butylate(2.77 mmol) in THF (5 ml) were slowly added 5 ml of a THF-solution of300 mg of ethyl isocyanoacetate (2.52 mmol) and 250 mg of cyclopropylisothiocyanate (2.52 mmol) at −20° C. The mixture was stirred for 15 minat −20° C. and was then allowed to warm to 0° C. in 1.5 h before 0.3 mlof acetic acid were added. The reaction mixture was concentrated invacuo to give a residue which was purified by flash columnchromatography (heptane/ethyl acetate 95:5 to 75:25) to give5-cyclopropylamino-thiazole-4-carboxylic acid ethyl ester (198 mg, 37%)as a yellow oil. MS (ISP) 213.1 (M+H)⁺.

b) Preparation of lithium 5-cyclopropylamino-thiazole-4-carboxylate

198 mg of 5-cyclopropylamino-thiazole-4-carboxylic acid ethyl ester(0.93 mmol) were dissolved in a 3:1 mixture of THF/methanol (2 ml) and1.4 ml of a 1N LiOH-solution were added. The reaction mixture wasstirred at RT for 3 days, then concentrated in vacuo and the remainingresidue was dried. This gave 191 mg of a yellow solid containing thecrude title compound (contaminated with excess of lithium hydroxide)that was used in the following step without further purification. MS(ISP) 182.9 (M−H)⁻.

EXAMPLE S21-D Preparation of5-cyclopropylamino-3-methyl-isothiazole-4-carboxylic acid ethyl ester a)Preparation of 3-amino-2-cyclopropylthiocarbamoyl-but-2-enoic acid ethylester

A mixture of 2.03 ml of ethyl 3-aminocrotonate (16 mmol) and 1.59 g ofcyclopropyl iso-thiocyanate (16 mmol) was heated to 100° C. for 5 h. Thereaction mixture was then cooled to 0° C. and diethyl ether (5 ml) and asmall amount of heptane were added. An oily precipitate formed and after5 min the solvents were decanted off. The remaining residue wastriturated with a small amount of diethyl ether at 0° C. The precipitatewas then filtered off and dried to give 1.64 g (45%) of3-amino-2-cyclopropylthiocarbamoyl-but-2-enoic acid ethyl ester as ayellow solid. ^(1H)NMR (DMSO-d₆, 300 MHz): δ 0.60 (m, 2H), 0.76 (m, 2H),1.11 (t, J=7.1 Hz, 3H), 1.90 (s, 3H), 3.28 (m, 1H), 3.97 (q, J=7.1 Hz,2H), 7.24 (br s, 1H), 8.21 (br s, 1H), 9.79 (d, J=5.5 Hz, 1H).

b) Preparation of 5-cyclopropylamino-3-methyl-isothiazole-4-carboxylicacid ethyl ester

To a vigorously stirred solution of 1 g of3-amino-2-cyclopropylthiocarbamoyl-but-2-enoic acid ethyl ester (4.4mmol) in chloroform (16 ml) was added dropwise a solution of 1.4 g ofbromine in chloroform (8 ml) at 0° C. After completion of the additionthe reaction mixture was stirred at 0° C. for additional 5 min. Thendiethyl ether and sat. NaHCO₃-solution were added and the mixture wasextracted with diethyl ether. The combined extracts were washed withbrine, dried (Na₂SO₄), filtered and concentrated in vacuo to give aresidue which was purified by flash column chromatography (100% DCM) togive 5-cyclopropylamino-3-methyl-isothiazole-4-carboxylic acid ethylester (410 mg, 40%) as a brown liquid. ^(1H)NMR (CDCl₃, 300 MHz): δ 0.73(m, 2H), 0.81 (m, 2H), 1.36 (t, J=7.2 Hz, 3H), 2.50 (s, 3H), 2.63 (m,1H), 4.29 (q, J=7.2 Hz, 2H), 7.80 (br s, 1H).

EXAMPLE S22-D Preparation of potassium;3-ethylamino-5-methyl-isoxazole-4-carboxylate

To a solution of 46 mg of 3-ethylamino-5-methyl-isoxazole-4-carboxylicacid ethyl ester (0.23 mmol) [synthesized as described in Synthesis1988, 203] were added 0.46 ml of a 1N KOH-solution and the mixture washeated to 80° C. for 2 h and then to 60° C. over night. Then allvolatile materials were removed in vacuo to give 54 mg of a white solidcontaining the crude title compound (contaminated with excess ofpotassium hydroxide) that was used in the following step without furtherpurification. ^(1H)NMR (DMSO-d₆, 300 MHz): δ 1.12 (t, J=7.1 Hz, 3H),2.37 (s, 3H), 3.07 (m, 2H), 6.83 (t, J=5.5 Hz, 1H).

EXAMPLE S23-D Preparation of potassium;1,3-dimethyl-5-methylamino-1H-pyrazole-4-carboxylate a) Preparation of3-methyl-5-methylamino-1H-pyrazole-4-carboxylic acid ethyl ester

A mixture of 1 g of 4-methylthiosemicarbazide (9.51 mmol) and 1.565 g ofethyl-2-chloro-acetoacetate (9.51 mmol) in THF (20 ml) was stirred for30 min at RT and then heated to reflux for 1 h. The yellow solid thatprecipitated was filtered off, washed with acetone and then dissolved inhot (95° C.) water. The precipitating sulfur was filtered off, theaqueous solution was cooled to 0° C., vigorously stirred and 5 ml of anaqueous ammonium hydroxide solution (25%) were added. A whiteprecipitate formed and the suspension was stirred for an additional hourat RT. The precipitate was then filtered off and dried to give 1.04 g(60%) of 3-methyl-5-methylamino-1H-pyrazole-4-carboxylic acid ethylester as a white solid. MS (ISP) 184.1 (M+H)⁺.

b) Preparation of 1,3-dimethyl-5-methylamino-1H-pyrazole-4-carboxylicacid ethyl ester

To a solution of 100 mg of3-methyl-5-methylamino-1H-pyrazole-4-carboxylic acid ethyl ester (0.55mmol) in methanol (5 ml) were added 52 mg of sodium hydroxide (1.3 mmol)and 77 mg of iodomethane (0.54 mmol) and the mixture was stirred at RTover night. The reaction mixture was then concentrated in vacuo at lowtemperature and 33 mg (31%) of1,3-dimethyl-5-methylamino-1H-pyrazole-4-carboxylic acid ethyl esterwere isolated from the remaining solid by HPLC (reversed phase,MeCN/water 20:80 to 50:50). MS (ISP) 198.2 (M+H)⁺.

c) Preparation of potassium;1,3-dimethyl-5-methylamino-1H-pyrazole-4-carboxylate

To a solution of 33 mg (0.17 mmol)1,3-dimethyl-5-methylamino-1H-pyrazole-4-carboxylic acid ethyl ester inTHF (0.5 ml) were added 330 μl of 1N potassium hydroxide solution. Themixture was heated to 50° C. for 3 h and then to reflux for 3 h. Thenall volatile materials were removed in vacuo to give a solid containingthe crude title compound (contaminated with excess of potassiumhydroxide) that was used in the following step without furtherpurification. MS (ISP) 168.1 (M−H)⁻.

EXAMPLE S24-D Preparation of 2-amino-5-chloro-3-iodo-benzoic acid a)Preparation of 2-amino-5-chloro-3-iodo-benzoic acid methyl ester

To a solution of 2-amino-5-chlorobenzoic acid methyl ester (1.10 g, 5.93mmol) in acetic acid (20 ml) was added N-iodosuccinimide (1.47 g, 6.52mmol) in small portions and the reaction mixture was stirred overnightat RT. The reaction mixture was diluted with ethylacetate and washedwith 1N NaOH solution, Na₂S₂O₃ solution, and brine, dried (MgSO₄),filtered and concentrated in vacuo to give a residue which was purifiedby flash column chromatography (EtOAc/cyclohexane 1:9-1:4) to give thedesired iodide (1.64 g, 89%) as a cream coloured solid. ^(1H) NMR(DMSO-d6, 300 MHz): δ 7.93 (d, J=2.5 Hz, 1H), 7.76 (d, J=2.5 Hz, 1H),6.73 (br s, 2H), 3.83 (s, 3H).

b) Preparation of 2-amino-5-chloro-3-iodo-benzoic acid

The title compound was prepared in analogy to5-chloro-2-isopropylamino-benzoic acid described in example S5-D.^(1H)-NMR (CDCl₃, 300 MHz): δ 7.94 (d, J=2.5 Hz, 1H), 7.83 (d, J=2.5 Hz,1H), 6.40 (br s, 2H).

EXAMPLE S25-D Preparation of 5-chloro-3-fluoro-2-methylaminobenzoic acida) Preparation of 3-fluoro-2-methylaminobenzoic acid ethyl ester

To a solution of 8-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione (200 mg,1.10 mmol) in DMF (2 ml) was added Na₂CO₃ (129 mg, 1.22 mmol), followedby methyl iodide (104 μl, 1.66 mmol) and the reaction mixture wasstirred at RT for 18 h. The reaction mixture was diluted with ethylacetate and the mixture was washed with water and brine. The organicphase was dried (MgSO₄), filtered and concentrated in vacuo to give8-fluoro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (190 mg, 88%) whichwas not purified due to its poor solubility but directly used in thefollowing step without further purification. To a suspension of theresidue (190 mg, 0.97 mmol) in ethanol (4 ml) was added DMAP (12 mg,0.09 mmol) and the reaction mixture was heated to reflux for 3 h. Thereaction mixture was cooled to RT and then concentrated in vacuo to givea residue which was partitioned between ethyl acetate and 0.1M HClsolution. The organic phase was washed with brine, dried over MgSO₄,filtered and concentrated in vacuo. The residue was purified by flashcolumn chromatography to give the desired product (132 mg, 69%) as alight yellow oil. ¹H NMR (CDCl₃, 300 MHz): 7.69 (aptd, J=8.0 Hz, 1H),7.50 (brds, 1H), 7.08 (ddd, J=14.0, 8.0, 1.5 Hz, 1H), 6.51 (aptdt,J=8.0, 4.5 Hz, 1H), 4.31 (q, J=7.0 Hz, 2H), 3.12 (m, 3H), 1.37 (t, J=7.0Hz, 3H).

b) Preparation of 5-chloro-3-fluoro-2-methylaminobenzoic acid ethylester

To a solution of 3-fluoro-2-methylaminobenzoic acid ethyl ester (124 mg,0.63 mmol) in acetic acid (4 ml) was added1,3-dichloro-5,5-dimethylhydantoin (93 mg, 0.47 mmol). The reactionmixture was stirred at RT for 3 h. The mixture was diluted with ethylacetate and then washed with sat. NaHCO₃. The organic phase was thenwashed with brine, dried (MgSO₄), filtered, and concentrated in vacuo togive a residue which was purified by flash column chromatography to give5-chloro-3-fluoro-2-methylaminobenzoic acid ethyl ester (135 mg, 93%) asa yellow oil. ¹H NMR (CDCl₃, 300 MHz): 7.67 (dd, J=2.5, 1.5 Hz, 1H),7.52 (brds, 1H), 7.09 (dd, J=13.5, 2.5 Hz, 1H), 4.31 (q, J=7.0 Hz, 2H),3.11 (m, 3H), 1.38 (t, J=7.0 Hz, 3H).

c) Preparation of 5-chloro-3-fluoro-2-methylaminobenzoic acid

To a solution of 5-chloro-3-fluoro-2-methylaminobenzoic acid ethyl ester(135 mg, 0.58 mmol) in MeOH was added 1N NaOH (1165 μl, 1.17 mmol) andthe reaction mixture was refluxed for 2 h. The reaction mixture wasdiluted with ethyl acetate and water and then extracted. The aqueouslayer was acidified to pH3 using 1N HCl and the aqueous layer wasextracted with EtOAc (2×). The organic layer was dried (MgSO₄), filteredand concentrated in vacuo to give the desired product (110 mg, 93%)which did not require further purification. MS (ISP) 202.1 (M−H)⁻.

EXAMPLE S26-D Preparation of 2-acetylamino-5-chloro-3-fluoro-benzoicacid a) Preparation of 5-chloro-2-diacetylamino-3-fluorobenzoic acidethyl ester

Acetic anhydride was added to 2-amino-5-chloro-3-fluoro-benzoic acidethyl ester (synthesized in analogy to a procedure described in exampleS25-D (230 mg, 1.06 mmol) followed by pyridine (213 μl, 2.64 mmol) andDMAP (65 mg, 0.53 mmol). The reaction mixture was heated to 65° C. for 4h. The reaction mixture was quenched with 1N HCl and then extracted withethyl acetate. The organic layers were combined, washed with sat. NaHCO₃and brine, dried (MgSO₄), filtered and concentrated in vacuo to give aresidue which was purified by flash column chromatography to the desiredproduct (185 mg, 58%) as a colourless liquid. ¹H NMR (CDCl₃, 300 MHz):7.89 (aptt, J=2.0 Hz, 1H), 7.43 (dd, J=8.5, 2.5 Hz, 1H), 4.33 (q, J=7.0Hz, 2H), 2.30 (s, 6H), 1.35 (t, J=7.0 Hz, 3H).

b) Preparation of 2-acetylamino-5-chloro-3-fluoro-benzoic acid

To a solution of 5-chloro-2-diacetylamino-3-fluorobenzoic acid ethylester (185 mg, 0.61 mmol) in MeOH (4 ml) was added 1N NaOH (1288 μl,1.29 mmol) and the reaction mixture was refluxed for 2 h. The reactionmixture was cooled to RT and then diluted with ethyl acetate and water.The organic phase was separated and the aqueous phase was made acidicwith 1N HCl to pH3 and then extracted with ethyl acetate (2×). Theorganic layer was dried (MgSO₄), filtered and concentrated in vacuo togive the desired product (130 mg, 92%) as a white solid which did notrequire further purification. MS (ISP) 230.1 (M−H)⁻.

EXAMPLE S27-D Preparation of 5-chloro-6-fluoro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione

To a suspension of NaH (49 mg, 1.11 mmol) in DMF (2 ml) at RT was addeda solution of 5-chloro-6-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione(synthesized in analogy to a procedure described in EP 59391) (200 mg,0.93 mmol) in DMF (2 ml). The mixture was stirred at RT for 1 h and thenmethyl iodide (87 μl, 1.39 mmol) was added. The reaction mixture wasthen warmed up to RT and stirring was continued overnight. The mixturewas quenched with water and extracted with ether. The organic phase waswashed with water and brine, dried (MgSO₄), filtered, and concentratedin vacuo to give a residue which was purified by flash columnchromatography (1:1 ethyl acetate:cyclohexane) to give the desiredcompound (83 mg, 39%) as a light yellow solid. ¹H NMR (CDCl₃, 300 MHz):7.56 (dd, J=9.5, 8.0 Hz, 1H), 7.10 (dd, J=9.5, 4.0 Hz, 1H), 3.59 (s,3H).

EXAMPLE S28-D Preparation of 6-amino-3-chloro-2-fluoro-benzoic acid and2-amino-3-chloro-6-fluoro-benzoic acid

A solution of 1 g (6.45 mmol) of 2-amino-6-fluoro-benzoic acid and 0.95g (7.09 mmol) of N-chlorosuccinimide in 10 ml acetic acid was stirred atRT for 17 hours. The resulting suspension was then concentrated invacuo, suspended in water and the pH was adjusted to 3 using a saturatedNaHCO₃ aqueous solution. The suspension was extracted twice with ethylacetate, and the combined organic phases were washed with brine, driedover magnesium sulfate, filtered and concentrated in vacuo. The residuewas purified by silicagel chromatography (eluent: ethyl acetate) leadingto 0.95 g of a mixture of 6-amino-3-chloro-2-fluoro-benzoic acid and2-amino-3-chloro-6-fluoro-benzoic acid. MS (ISP) 187.9 (M−H)⁻.

EXAMPLE S29-D Preparation of 2-amino-3,5-dichloro-6-fluoro-benzoic acid

A solution of 1.2 g (6.33 mmol) of 2-amino-6-fluoro-benzoic acid and 1.9g (14.23 mmol) of N-chlorosuccinimide in 10 ml acetic acid was stirredat RT for 17 hours. 0.55 g of 1,3-dichloro-5,5-dimethylhydantoin (1.9mmol) were added. After two hours stirring the suspension wasconcentrated in vacuo, suspended in water, stirred for 30 min andfiltered leading after drying under high vacuo to 0.8 g (54%) of2-amino-3,5-dichloro-6-fluoro-benzoic acid as a light yellow powder. MS225 (M).

EXAMPLE S30-D Preparation of 6-chloro-1-cyclopropylmethyl-1H-benzo[d][1,3]oxazine-2,4-dione

The title compound was prepared in analogy to of6-chloro-1-methyl-1H-benzo[d][1,3]-oxazine-2,4-dione described inexample S1-D. ^(1H)NMR (DMSO-d₆, 300 MHz): δ 0.42-0.54 (m, 4H), 1.17 (m,1H), 3.96 (d, J=6.9 Hz, 2H), 7.63 (d, J=9.0 Hz, 1H), 7.88 (dd, J=9.0 and2.5 Hz, 1H), 7.97 (d, J=2.5 Hz, 1H).

EXAMPLE S31-D Preparation of 3-chloro-2-fluoro-6-methylamino-benzoicacid (S31-D1) a) Preparation of (4-chloro-3-fluoro-phenyl)-methyl-amine

Formic acid (1.76 ml) was added to acetic acid anhydride (0.91 ml) at 0°C. The solution was stirred for 10 min at this temperature. The reactionwas heated under nitrogen to 55° C. for 2 h. The reaction mixture wascooled to 0° C. 4-Chloro-3-fluoroaniline (1.07 g) dissolved in THF (2ml) was added and the reaction was stirred over night at RT. The solventwas evaporated in vacuo. The residue was dissolved in THF (4 ml). Thesolution was cooled to 0° C. and borane tetrahydrofuran complex 1M inTHF (16.2 ml) was added slowly. Strong gas evolution was observed. Thereaction was heated to reflux for 3 h, then cooled to 0° C. and MeOH (4ml) was added dropwise. The reaction was stirred for 1 h and 1M aq HClsolution (6 ml) was added. The reaction was stirred over night at RT.The solvent was removed in vacuo and the pH of the aqueous layer wasadjusted to 9 with 2N aq NaOH solution. The reaction mixture wasextracted twice with diethyl ether and the combined organic layers weredried over sodium sulfate, filtered and the solvent was removed in vacuoto yield (4-chloro-3-fluoro-phenyl)-methyl-amine (1150 mg, 98%) as alight brown oil. ^(1H)NMR (DMSO-d₆, 300 MHz): δ 2.65 (d, J=5.1 Hz, 3H),6.15 (d, J=5.1 Hz, 1H), 6.20 (dd, J=3.0 and J=8.4 Hz, 1H), 6.45 (dd,J=2.4 and 12.3 Hz, 1H), 7.18 (t, J=8.7 Hz, 1H).

b) Preparation of 3-chloro-2-fluoro-6-methylamino-benzoic acid

n-Butyllithium solution (1.6 M in hexane, 4.95 mL, 8.0 mmol) was addedat −78° C. to THF (10 ml) under nitrogen. A solution of(4-chloro-3-fluoro-phenyl)-methyl-amine (575 mg, 4.0 mmol) in THF (3 mL)was added dropwise keeping the temperature below −70° C. The solutionwas stirred for 5 min at −75° C. Potassium tert-butylate (889 mg, 8mmol) dissolved in THF (2 ml) was added within 15 min. The reaction wasstirred at −75° C. for 2 h and treated with a large excess of dry ice.Within 30 min the reaction was warmed to RT. Water was added and thereaction was extracted twice with diethyl ether. The aqueous layer wasacidified to pH1 with 1N aq. HCl solution and extracted twice withdiethyl ether. The combined organic layers were washed with sat. aq.NaCl solution, dried over sodium sulfate, filtered and the solvent wasremoved in vacuo to yield 3-chloro-2-fluoro-6-methylamino-benzoic acid(83 mg, 11%). Light brown solid, ^(1H)NMR (DMSO-d₆, 300 MHz): δ 81 (s,3H), 6.52 (d, J=9.2 Hz, 1H), 7.45 (t, J=9.1 Hz, 1H).

Ex. Name * MS (ISP) S31-D2 5-Chloro-2-ethylamino-nicotinic acid S6-D199.0 (M − H)⁻ S31-D3 5-Chloro-2-cyclopropylamino-nicotinic acid S6-D211.0 (M − H)⁻ S31-D4 5-Bromo-2-methylamino-nicotinic acid S6-D 228.9 (M− H)⁻ S31-D5 5-Bromo-2-ethylamino-nicotinic acid S6-D 243.1 (M − H)⁻S31-D6 5-Fluoro-2-methylamino-nicotinic acid S6-D 169.1 (M − H)⁻ S31-D72-Ethylamino-5-fluoro-nicotinic acid S6-D 183.1 (M − H)⁻ S31-D85-Methyl-2-methylamino-nicotinic acid S6-D 167.2 (M + H)⁺ S31-D92-Ethylamino-5-methyl-nicotinic acid S6-D 181.1 (M + H)⁺ S31-D106-Chloro-3-ethylamino-pyridine-2-carboxylic acid S7-D 199.1 (M − H)⁻S31-D11 6-Chloro-3-cyclopropylamino-pyridine-2-carboxylic S7-D 211.0 (M− H)⁻ acid S31-D12 Potassium; 4-methylamino-thiophene-3-carboxylateS19-D 156.0 (M − H)⁻ S31-D13 Potassium;2-methylamino-thiophene-3-carboxylate S19-D 156.0 (M − H)⁻ S31-D143-Methyl-5-methylamino-isothiazole-4-carboxylic S21-D 201.2 (M + H)⁺acid ethyl ester S31-D15 5-Ethylamino-3-methyl-isothiazole-4-carboxylicS21-D 215.2 (M + H)^(+−(?)) acid ethyl ester S31-D165-Isopropylamino-3-methyl-isothiazole-4- S21-D 229.3 (M + H)⁺ carboxylicacid ethyl ester *: Prepared in analogy to exampleAmides: (Compound of Formula VI)

EXAMPLE S1-E Preparation ofN-(4-tert-butyl-benzyl)-2,5-dichloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-nicotinamide(S1-E1)

A solution of 2,5-dichloronicotinic acid (300 mg, 1.56 mmol),(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amine (578 mg,1.72 mmol), 4-methylmorpholine (474 mg, 7.81 mmol), and HBTU (889 mg,2.34 mmol) in DMF (9 mL) was stirred at RT for 16 h, then partitionedbetween heptane, ethyl acetate and water. The organic layer was washedwith brine, dried (MgSO₄), and evaporated. Chromatography (SiO₂,heptane-ethyl acetate gradient) afforded the title compound (761 mg,95%). White foam, MS (ISP) 509.0 (M+H)⁺.

Ex. Name * MS (ISP) S1-E2N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- S1-E 459.3 (M + H)⁺ethyl]-2-fluoro-nicotinamide S1-E3N-(4-tert-Butyl-benzyl)-4-chloro-N-[2-(3,4-dichloro- S1-E 475.2 (M + H)⁺phenyl)-ethyl]-nicotinamide S1-E4N-(4-tert-Butyl-benzyl)-4-chloro-N-[2-(3-trifluoromethyl- S1-E 475.3(M + H)⁺ phenyl)-ethyl]-nicotinamide S1-E55-Bromo-N-(4-tert-butyl-benzyl)-2-chloro-N-[2-(3,4- S1-E 553.0 (M + H)⁺dichloro-phenyl)-ethyl]-nicotinamide S1-E6N-(4-tert-Butyl-benzyl)-2-chloro-N-[2-(3,4-dichloro- S1-E 493.3 (M + H)⁺phenyl)-ethyl]-5-fluoro-nicotinamide *: Prepared in analogy to exampleFinal Compounds: (Compounds of Formula I)

EXAMPLE 1 Preparation of5-chloro-N-(4-cyclopentyl-benzyl)-2-isopropylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide

To a solution of 50 mg of 5-chloro-2-isopropylamino-benzoic acid (0.23mmol) and 81 mg (0.23 mmol) of(4-cyclopentyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amine in 4ml of DMF were added 75 mg of TBTU (0.23 mmol) and 0.2 ml (1.17 mmol) ofN,N-di-isopropylethyl amine. After stirring the reaction mixture overnight at RT it was diluted with 50 ml water and extracted with ethylacetate. The combined organic phases were washed with 10%-aqueous KHCO₃solution, 0.1M HCl solution and brine, dried with magnesium sulfate,filtered and concentrated in vacuo. The remaining oil was purified bycolumn chromatography (silica gel; heptane 100% to heptane/EtOAc 4:1) togive 90 mg (71%) of a colorless oil. MS (ISP) 543.5 (M+H)⁺.

EXAMPLE 2 Preparation ofN-(4-tert-butyl-benzyl)-N-2-(3,4-dichloro-phenyl)-ethyl-2-methylamino-nicotinamide

A mixture ofN-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-fluoro-nicotinamide(100 mg, 0.22 mmol), 41% aq. methylamine solution (1 mL) and THF (1 mL)was heated under microwave irradiation for 1 h at 100° C., thenpartitioned between ethyl acetate and water. The organic layer waswashed with brine, dried (MgSO₄), and evaporated to produce the titlecompound (102 mg, 95%). Colourless gum, MS (ISP) 470.4 (M+H)⁺.

EXAMPLE 3 Preparation of 6-methyl-3-methylamino-pyridine-2-carboxylicacid [2-(4-chloro-phenyl)-ethyl]-(4-cyclobutyl-benzyl)-amide

A mixture of 3-amino-6-methyl-pyridine-2-carboxylic acid[2-(4-chloro-phenyl)-ethyl]-(4-cyclobutyl-benzyl)-amide (151 mg, 0.348mmol), 37% aq. formaldehyde solution (0.16 mL, 2.09 mmol) and ethanol (2mL) was stirred at 50° C. for 3 h, then after removal of volatilematerial by distillation, sodium borohydride (55 mg, 1.39 mmol) wasadded, and stirring at 50° C. was continued over 3 h. After cooling, thereaction mixture was partitioned between ethyl acetate and water, theorganic layer was washed with brine, dried (MgSO₄), and evaporated.Chromatography (SiO₂, heptane-ethyl acetate gradient) produced the titlecompound (126 mg, 81%). Colourless gum, MS (ISP) 448.3 (M+H)⁺.

EXAMPLE 4 Preparation ofN-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-5-ethyl-2-methylamino-nicotinamide

A mixture of 5-ethyl-2-methylamino-nicotinic acid ethyl ester (40 mg,0.19 mmol), 2 M aq. potassium hydroxide solution (0.19 mL, 0.38 mmol)and THF was heated at 60° C. for 16 h, then evaporated to dryness. Theresidue was taken up in DMF (3.2 mL) and treated with(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amine (71 mg, 0.21mmol), HBTU (109 mg, 0.29 mmol), and 4-methylmorpholine (58 mg, 0.57mmol). The homogeneous solution was stirred at RT for 16 h, thenpartitioned between water and ethyl acetate. The organic layer waswashed with brine, dried (MgSO₄), and evaporated. Chromatography (SiO₂,heptane-ethyl acetate gradient) produced the title compound (77 mg,80%). Light yellow oil, MS (ISP) 498.4 (M+H)⁺.

EXAMPLE 5N-(4-tert-butylbenzyl)-2-chloro-N-[2-(3,4-dichlorophenyl)-ethyl]-3-fluoro-6-methylaminobenzamide

A mixture of5-chloro-6-fluoro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione (83 mg,0.36 mmol) and(4-tert-butylbenzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amine (122 mg, 0.36mmol) in DMF (2 ml) was heated to 140° C. for 2 h and then at 110° C.overnight. The reaction mixture was then cooled to RT and the mixturewas diluted with ethyl acetate and washed with water and brine. Theorganic layer was dried (MgSO₄), filtered and concentrated in vacuo togive a residue which was purified by flash column chromatography to givethe desired product (51 mg, 27%) as a white solid. MS (ISP) 521.9(M+H)⁺.

EXAMPLE 62-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide

2-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide(140 mg, 0.286 mmol) was dissolved in methylene chloride (2 ml). Aceticacid anhydride (32 mg, 0.315 mmol) and ethyl-diisopropylamine (41 mg,0.315 mmol) were added and the reaction was stirred over night at RT.Further acetic acid anhydride (30 μl) was added and the reaction wasstirred for another night at RT. The reaction was extracted with ethylacetate, the combined organic layers were concentrated in vacuo and theresidue was purified by flash column chromatography (heptane/ethylacetate:7/3) to yield the desired product (110 mg, 72%) as an off-whitesolid. MS (ISP) 529.2 (M−H)⁻.

EXAMPLE 75-Chloro-N-(4-cyclopropyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide

To a solution of 53 mg of 2-amino-5-chloro-benzoic acid (0.33 mmol) and105 mg (0.33 mmol) of(4-cyclopropyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amine in 4.5ml of DMF were added 171 mg of HBTU (0.45 mmol) and 0.1 ml (0.9 mmol) of4-methyl-morpholine. After stirring the reaction mixture over night atRT it was diluted with 50 ml water and extracted with ethyl acetate. Thecombined organic phases were washed with 10% aqueous KHCO₃ solution,0.1M HCl solution and brine, dried with magnesium sulfate, filtered andconcentrated in vacuo. The remaining oil was purified by columnchromatography (silica gel; heptane/EtOAc 6:1) to give 127 mg (88%) of2-amino-5-chloro-N-(4-cyclopropyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamideas a yellow oil. MS (ISP) 473 (M+H)⁺.

The complete amount (127 mg, 0.27 mmol) was dissolved in 2.5 ml DCMunder argon and cooled down to −10° C. Then 0.057 ml of trifluoroaceticacid anhydride (0.4 mmol) and 0.065 ml pyridine (0.8 mmol) were addedand the reaction mixture was stirred for 2 h at RT. The reaction mixturewas poured on 1.5 ml 1 N aqueous HCl and the organic phase was separatedand washed with brine. The aqueous phases were reextracted with DCM, andthe combined organic phases were dried over magnesium sulfate, filteredand concentrated in vacuo to give 151 mg (98%) of5-chloro-N-(4-cyclopropyl-benzyl)-2-(2,2,2-trifluoro-acetylamino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamideas a light yellow solid. MS (ISP) 569.2 (M+H)⁺.

50 mg of5-chloro-N-(4-cyclopropyl-benzyl)-2-(2,2,2-trifluoro-acetylamino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide(0.09 mmol) were dissolved in 1 ml DMF and 0.1 ml DMPU(1,3-dimethyl-3,4,5,6-tetrahydro-2-pyridinon) under argon and cooleddown to 0° C. 6 mg of sodium hydride (55% dispersion in oil, 0.135 mmol)were then added and after 15 min stirring at RT the reaction mixture wasagain cooled down to 0° C. 0.008 ml of methyl iodide (0.135 mmol) wereadded and after 4 h stirring at RT a second portion of the same amountwas added. After 20 hours stirring at RT the reaction mixture wasdiluted with ethyl acetate and washed with water and brine. The aqueousphases were reextracted with ethyl acetate, and the combined organicphases were dried over magnesium sulfate, filtered off and concentratedin vacuo. The residue was purified by column chromatography (silica gel;heptane/EtOAc 9:1) to give 36 mg (70%)5-chloro-N-(4-cyclopropyl-benzyl)-2-[methyl-(2,2,2-trifluoro-acetyl)-amino]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamideas a colorless viscous oil. MS (ISP) 583.2 (M+H)⁺.

35 mg of5-chloro-N-(4-cyclopropyl-benzyl)-2-[methyl-(2,2,2-trifluoro-acetyl)-amino]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamidewere dissolved in 1 ml methanol and 0.06 ml 1N aqueous NaOH and heatedto 55° C. for 5 hours. The mixture was then concentrated in vacuo,diluted with ethyl acetate and washed with water and brine. The organicphase was dried over magnesium sulfate, filtered off and concentrated invacuo, to give 28 mg (96%)5-chloro-N-(4-cyclopropyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamideas a light yellow viscous oil. (ISP) 503.1 (M+H)⁺.

EXAMPLE 8(2-{(4-tert-Butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)-aceticacid

A solution of 33 mg of(2-{(4-tert-butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)-aceticacid ethyl ester (0.06 mmol) in 0.5 ml methanol and 0.11 ml 1N aqueousNaOH was heated for 2 hours to 50° C. After cooling down to RT themixture was neutralized with 0.11 ml 1N aqueous HCl, treated with asmall amount of water, and extracted twice with ethylacetate. Thecombined organic phases were washed with brine, dried over magnesiumsulfate, filtered and concentrated in vacuo to give 26 mg (79%) of thetitle compound as an off-white solid. MS (ISP) 563.4 (M+H)⁺.

EXAMPLE 95-Chloro-2-methylamino-N-[4-(3,3,3-trifluoro-2-hydroxy-propoxy)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide

A solution of 930 mg (1.68 mmol) ofN-(4-benzyloxy-benzyl)-5-chloro-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide(2 mmol) in 30 ml ethylacetate was hydrogenated over 300 mg of 5% Pd—Cfor 4 hours at RT. After completion of the reaction, the suspension wasfiltered, the catalyst washed with additional ethyl acetate and thefiltrate was concentrated in vacuo. The residue was purified by columnchromatography (silica gel; heptane/-EtOAc 3:1) to give 339 mg5-chloro-N-(4-hydroxy-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide(75%) as a white foam. MS (ISP) 463 (M+H)⁺.

A suspension of 80 mg (0.17 mmol) of5-chloro-N-(4-hydroxy-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide,40 mg (0.21 mmol) 3-bromo-1,1,1-trifluoro-2-propanol and 57 mg (0.41mmol) of potassium carbonate in 3 ml DMF was stirred at RT for 65 hours.The reaction mixture was then diluted with 15 ml water and 15 ml brine,and extracted twice with ethylacetate. The combined organic layers werewashed with brine, dried over magnesium sulfate, filtered andconcentrated in vacuo. The residue was purified by column chromatography(silica gel; DCM/EtOAc 97:3) to give 58 mg of5-chloro-2-methylamino-N-[4-(3,3,3-trifluoro-2-hydroxy-propoxy)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide(55%) as a light yellow viscous oil. MS (ISP) 575.3 (M+H)⁺.

EXAMPLE 10N-(4-tert-Butyl-benzyl)-5-chloro-2-(3-hydroxy-propylamino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamideand3-(2-{(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)-propionicacid

A solution of 150 mg (0.31 mmol) of2-amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamideand 76 mg (0.46 mmol) of formylpropionic acid ethylester (prepared bystirring 3,3-diethoxypropionic acid ethylester at RT with 1N—HClfollowed by extraction with diethylether and concentration in vacuo) in3 ml EtOH was refluxed for two hours. The reaction mixture was cooleddown to RT and reacted with 17 mg (0.46 mmol) of sodium borohydride.After 5 min at RT and 30 min under reflux additional 9 mg (0.29 mmol) ofsodium borohydride were added followed by 5 min at RT and 30 min underreflux. The reaction mixture was then concentrated, treated withdiethylether and 2 drops 1N—HCl, and extracted twice with ethylacetate.The combined organic layers were washed with brine, dried over magnesiumsulfate, filtered and concentrated in vacuo. The residue was purified bycolumn chromatography (silica gel; heptane/EtOAc 90:10 to 50:50) to give53 mg (28%) of3-(2-{(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)-propionicacid ethyl ester as a light yellow viscous oil [MS (ISP) 489.4 (M+H)⁺]and 12 mg (7%) ofN-(4-tert-butyl-benzyl)-5-chloro-2-(3-hydroxy-propylamino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamideas light yellow amorphous solid [MS (ISP) 547.4 (M+H)⁺]. A solution of42 mg (0.07 mmol) of3-(2-{(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)-propionicacid ethyl ester in 1 ml EtOH and 0.14 ml 1N-NaOH was stirred at 50° C.for 17 hours. The reaction mixture was concentrated in vacuo, treatedwith water and the pH was adjusted to 3 with 1N—HCl. The mixture wasextracted twice with diethylether, washed with brine, dried overmagnesium sulfate, filtered and concentrated in vacuo to give 39 mg(93%) of3-(2-{(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)-propionicacid as an off-white foam. MS (ISP) 561.5 (M+H)⁺.

EXAMPLE 112-Amino-3-bromo-N-(4-tert-butyl-benzyl)-5-methyl-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide

2-Amino-N-(4-tert-butyl-benzyl)-5-methyl-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide(60 mg, 0.128 mmol) was dissolved in acetonitrile (2 ml) andN-bromosuccinimide (23 mg, 0.128 mmol) was added. The reaction washeated to 75° C. for 4 h. The reaction mixture was cooled to RT andpartitionated between water and methylene chloride. The aqueous layerwas extracted with methylene chloride and the combined organic phase wasdried (MgSO₄), filtered and concentrated in vacuo to give the desiredproduct (50 mg, 71%) as a light brown oil. MS (ISP) 547.3 (M+H)⁺.

EXAMPLE 122-Amino-N-(4-tert-butyl-benzyl)-3-chloro-5-methyl-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide

2-Amino-N-(4-tert-butyl-benzyl)-5-methyl-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide(60 mg, 0.128 mmol) was dissolved in acetonitrile (2 ml) andN-chlorosuccinimide (23 mg, 0.128 mmol) was added. The reaction washeated to 95° C. for 4 h. The reaction mixture was cooled to RT andpartitionated between water and methylene chloride. The aqueous layerwas extracted with methylene chloride and the combined organic phase wasdried (MgSO₄), filtered and concentrated in vacuo to give a residuewhich was purified by flash column chromatography (heptane/ethyl acetate7:3) to yield the desired product (18 mg, 28%) as a brown gum. MS (ISP)503.3 (M+H)⁺.

EXAMPLE 13N-(4-tert-Butyl-benzyl)-5-chloro-2-(cyanomethyl-amino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide(13.1)

2-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide(80 mg, 0.164 mmol), bromo-acetonitrile (21 mg, 0.172 mmol) and sodiumhydrogen catbonat (17 mg, 01.96 mmol) were suspended in ethanol (21 ml)and heated to 100° C. for 3 days. The reaction mixture was cooled to RT,filtered and the precipitate was washed with ethanol. The solvent of thefiltrate was concentrated in vacuo to give a residue which was purifiedby flash column chromatography (heptane/ethyl acetate 7:3) to yield thedesired product (26 mg, 30%) as a yellow solid. MS (ISP) 526.2 (M−H)⁻.

Ex. Name * MS (ISP) 13.2 6-Chloro-3-methylamino-pyridine-2-carboxylicacid (4- 1 471.2 (M + H)⁺tert-butyl-benzyl)-[2-(2-chloro-pyridin-4-yl)-ethyl]- amide 13.3N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(2-chloro- 1 471.2 (M + H)⁺pyridin-4-yl)-ethyl]-2-methylamino-nicotinamide 13.4N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(2-chloro- 1 470.4 (M + H)⁺pyridin-4-yl)-ethyl]-2-methylamino-benzamide 13.55-Chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2-isopropyl- 1 543.2 (M + H)⁺amino-N-(4-pentafluoroethyl-benzyl)-benzamide 13.65-Chloro-2-isopropylamino-N-[4-(1,2,2,2-tetrafluoro-1- 1 643.0 (M + H)⁺trifluoromethyl-ethyl)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.75-Chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2-isopropyl- 1 593.3 (M + H)⁺amino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide 13.85-Chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-2- 1 643.2 (M + H)⁺isopropylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide 13.95-Chloro-2-isopropylamino-N-(4-pentafluoroethyl- 1 609.3 (M + H)⁺benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]- benzamide 13.10N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 1 505.3 (M + H)⁺(4-trifluoromethyl-pyridin-2-yl)-ethyl]-nicotinamide 13.11N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 1 504.3 (M + H)⁺(4-trifluoromethyl-pyridin-2-yl)-ethyl]-benzamide 13.126-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 505.1 (M + H)⁺tert-butyl-benzyl)-[2-(5-trifluoromethyl-pyridin-2-yl)- ethyl]-amide13.13 N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 1 504.1 (M +H)⁺ (5-trifluoromethyl-pyridin-2-yl)-ethyl]-benzamide 13.146-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 505.3 (M + H)⁺tert-butyl-benzyl)-[2-(6-trifluoromethyl-pyridin-2-yl)- ethyl]-amide13.15 N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 1 505.4 (M +H)⁺ (6-trifluoromethyl-pyridin-2-yl)-ethyl]-nicotinamide 13.16N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 1 504.3 (M + H)⁺(6-trifluoromethyl-pyridin-2-yl)-ethyl]-benzamide 13.175-Chloro-N-(4-cyclobutyl-benzyl)-N-[2-(3,4-dichloro- 1 529.3 (M + H)⁺phenyl)-ethyl]-2-isopropylamino-benzamide 13.185-Chloro-N-(4-cyclobutyl-benzyl)-2-isopropylamino-N- 1 529.4 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.19N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(5-chloro- 1 470.4 (M + H)⁺pyridin-2-yl)-ethyl]-2-methylamino-benzamide 13.205-Chloro-N-[4-(1-fluoro-cyclobutyl)-benzyl]-2-methyl- 1 519.4 (M + H)⁺amino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.215-Chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-N-[4-(1- 1 519.2 (M + H)⁺fluoro-cyclobutyl)-benzyl]-2-methylamino-benzamide 13.225-Chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-N-[4-(1- 1 532.1 (M + H)⁺methoxy-cyclobutyl)-benzyl]-2-methylamino- nicotinamide 13.23N-(4-tert-Butyl-benzyl)-5-chloro-2-cyclopropylamino- 1 529.3 (M + H)⁺N-[2-(3,4-dichloro-phenyl)-ethyl]-benzamide 13.24N-(4-tert-Butyl-benzyl)-5-chloro-2-cyclopropylamino- 1 529.3 (M + H)⁺N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.25N-(4-Cyclobutyl-benzyl)-2-cyclopropylamino-5- 1 561.3 (M + H)⁺trifluoromethyl-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.265-Chloro-N-(4-cyclobutyl-benzyl)-N-[2-(3,4-dichloro- 1 515.3 (M + H)⁺phenyl)-ethyl]-2-ethylamino-benzamide 13.275-Chloro-N-(4-cyclobutyl-benzyl)-2-ethylamino-N-[2- 1 515.1 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.285-Chloro-N-(4-cyclopentyl-benzyl)-2-ethylamino-N-[2- 1 529.3 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.295-Chloro-N-(4-cyclobutyl-benzyl)-2-ethylamino-N-[2- 1 533.2 (M + H)⁺(4-fluoro-3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.305-Chloro-N-(4-cyclopentyl-benzyl)-N-[2-(3,4-dichloro- 1 529.3 (M + H)⁺phenyl)-ethyl]-2-ethylamino-benzamide 13.315-Chloro-N-(4-cyclopentyl-benzyl)-2-ethylamino-N-[2- 1 547.3 (M + H)⁺(4-fluoro-3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.32N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro-3-tri- 1 527.2 (M + H)⁺fluoromethyl-pyrazol-1-yl)-ethyl]-2-methylamino-benzamide 13.33N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 1 501.2 (M + H)⁺(3-phenyl-pyrazol-1-yl)-ethyl]-benzamide 13.34N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro-5- 1 542.3 (M + H)⁺methyl-3-trifluoromethyl-pyrazol-1-yl)-ethyl]-2-methylamino-nicotinamide 13.35N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro-3- 1 541.5 (M + H)⁺methyl-5-trifluoromethyl-pyrazol-1-yl)-ethyl]-2- methylamino-benzamide13.36 N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro-5- 1 541.3 (M +H)⁺ methyl-3-trifluoromethyl-pyrazol-1-yl)-ethyl]-2-methylamino-benzamide 13.37N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 1 494.4 (M + H)⁺(4-trifluoromethyl-imidazol-1-yl)-ethyl]-nicotinamide 13.38N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 1 493.4 (M + H)⁺(4-trifluoromethyl-imidazol-1-yl)-ethyl]-benzamide 13.39N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 1 507.4 (M + H)⁺(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethyl]- benzamide 13.40N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 1 493.1 (M + H)⁺(3-trifluoromethyl-pyrazol-1-yl)-ethyl]-benzamide 13.41N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 1 493.4 (M + H)⁺(5-trifluoromethyl-pyrazol-1-yl)-ethyl]-benzamide 13.423-Ethylamino-5-methyl-isoxazole-4-carboxylic acid (4- 1 488.1 (M + H)⁺tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.431,3-Dimethyl-5-methylamino-1H-pyrazole-4-carboxylic 1 487.3 (M + H)⁺acid (4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)- ethyl]-amide 13.445-Ethylamino-3-methyl-isothiazole-4-carboxylic acid (4- 4 504.0 (M + H)⁺tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.453-Methyl-5-methylamino-isothiazole-4-carboxylic acid 4 490.3 (M + H)⁺(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)- ethyl]-amide 13.463-Methyl-5-methylamino-isothiazole-4-caboxylic acid 4 490.3 (M + H)⁺(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]- amide 13.475-Cyclopropylamino-3-methyl-isothiazole-4-carboxylic 4 516.3 (M + H)⁺acid (4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)- ethyl]-amide 13.485-Cyclopropylamino-3-methyl-isothiazole-4-carboxylic 4 516.3 (M + H)⁺acid (4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)- ethyl]-amide13.49 5-Isopropylamino-3-methyl-isothiazole-4-carboxylic 4 518.5 (M +H)⁺ acid (4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide 13.50 5-Isopropylamino-3-methyl-isothiazole-4-carboxylic 4518.2 (M + H)⁺ acid (4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.51 5-Cyclopropylamino-thiazole-4-carboxylic acid(4-tert- 1 502.3 (M + H)⁺butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.522-Methylamino-thiophene-3-carboxylic acid (4-tert- 1 475.2 (M + H)⁺butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.533-Methylamino-thiophene-2-carboxylic acid (4-tert- 1 475.2 (M + H)⁺butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.543-Methylamino-thiophene-2-carboxylic acid (4-tert- 1 475.2 (M + H)⁺butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.554-Methylamino-thiophene-3-carboxylic acid (4-tert- 1 475.1 (M + H)⁺butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.564-Methylamino-thiophene-3-carboxylic acid (4-tert- 1 475.0 (M + H)⁺butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.574-Acetylamino-N-(4-tert-butyl-benzyl)-N-[2-(3,4-di- 1 498.2 (M + H)⁺chloro-phenyl)-ethyl]-nicotinamide 13.584-Acetylamino-N-(4-tert-butyl-benzyl)-N-[2-(4-chloro- 1 532.1 (M + H)⁺3-trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.594-Acetylamino-N-(4-tert-butyl-benzyl)-N-[2-(3- 1 498.2 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.603-Amino-pyridine-2-carboxylic acid (4-tert-butyl- 1 456.1 (M + H)⁺benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.613-Acetylamino-pyridine-2-carboxylic acid (4-tert-butyl- 1 498.4 (M + H)⁺benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.622-Amino-N-(4-tert-butyl-benzyl)-N-[2-(4-chloro-3-tri- 1 490.3 (M + H)⁺fluoromethyl-phenyl)-ethyl]-nicotinamide 13.632-Amino-N-(4-tert-butyl-benzyl)-N-[2-(3- 1 456.5 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.643-Methylamino-pyridine-2-carboxylic acid (4-tert-butyl- 3 470.1 (M + H)⁺benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.653-Amino-pyridine-2-carboxylic acid (4-tert-butyl- 1 456.5 (M + H)⁺benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide 13.663-Methylamino-pyridine-2-carboxylic acid (4-tert-butyl- 3 470.5 (M + H)⁺benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide 13.673-Amino-6-methyl-pyridine-2-carboxylic acid (4-tert- 1 470.4 (M + H)⁺butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.686-Methyl-3-methylamino-pyridine-2-carboxylic acid (4- 3 484.5 (M + H)⁺tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.69N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 2 484.5 (M + H)⁺ethyl-2-ethylamino-nicotinamide 13.70N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 2 484.5 (M + H)⁺ethyl-2-dimethylamino-nicotinamide 13.71N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 2 470.1 (M + H)⁺ethyl]-4-methylamino-nicotinamide 13.72N-(4-tert-Butyl-benzyl)-2-cyclopropylamino-N-[2-(3,4- 2 496.5 (M + H)⁺dichloro-phenyl)-ethyl]-nicotinamide 13.73N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 2 484.2 (M + H)⁺ethyl]-4-ethylamino-nicotinamide 13.74N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3,4-dichloro- 2 504.3 (M + H)⁺phenyl)-ethyl]-2-methylamino-nicotinamide 13.755-Bromo-N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro- 2 548.2 (M + H)⁺phenyl)-ethyl]-2-methylamino-nicotinamide 13.765-Bromo-N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro- 2 562.3 (M + H)⁺phenyl)-ethyl]-2-ethylamino-nicotinamide 13.77N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 2 500.3 (M + H)⁺ethyl]-2-(2-hydroxy-ethylamino)-nicotinamide 13.78N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3,4-dichloro- 2 518.3 (M + H)⁺phenyl)-ethyl]-2-ethylamino-nicotinamide 13.79N-(4-tert-Butyl-benzyl)-5-chloro-2-cyclopropylamino- 2 530.3 (M + H)⁺N-[2-(3,4-dichloro-phenyl)-ethyl]-nicotinamide 13.80N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 2 488.1 (M + H)⁺ethyl]-5-fluoro-2-methylamino-nicotinamide 13.81N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3,4-dichloro- 2 534.3 (M + H)⁺phenyl)-ethyl]-2-(2-hydroxy-ethylamino)-nicotinamide 13.823-Amino-N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro- 1 456.4 (M + H)⁺phenyl)-ethyl]-isonicotinamide 13.83 3-Amino-pyrazine-2-carboxylic acid(4-tert-butyl- 1 457.4 (M + H)⁺benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.84N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 2 540.4 (M + H)⁺ethyl]-2-((R)-2-hydroxymethyl-pyrrolidin-1-yl)- nicotinamide 13.85N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 2 510.5 (M + H)⁺ethyl]-2-pyrrolidin-1-yl-nicotinamide 13.86N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 3 470.4 (M + H)⁺ethyl]-3-methylamino-isonicotinamide 13.873-Methylamino-pyrazine-2-carboxylic acid (4-tert-butyl- 3 471.2 (M + H)⁺benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.88N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 2 502.2 (M + H)⁺ethyl]-2-ethylamino-5-fluoro-nicotinamide 13.89N-(4-tert-Butyl-benzyl)-2-cyclopropylamino-N-[2-(3,4- 2 514.4 (M + H)⁺dichloro-phenyl)-ethyl]-5-fluoro-nicotinamide 13.902-Azetidin-1-yl-N-(4-tert-butyl-benzyl)-N-[2-(3,4-di- 2 496.4 (M + H)⁺chloro-phenyl)-ethyl]-nicotinamide 13.91 4-Amino-pyrimidine-5-carboxylicacid (4-tert-butyl- 1 457.4 (M + H)⁺benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.922-Amino-N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro- 1 470.4 (M + H)⁺phenyl)-ethyl]-6-methyl-nicotinamide 13.934-Methylamino-pyrimidine-5-carboxylic acid (4-tert- 3 471.2 (M + H)⁺butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.94N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 3 484.5 (M + H)⁺ethyl]-6-methyl-2-methylamino-nicotinamide 13.956-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 504.3 (M + H)⁺tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.965-Chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methyl- 1 616.3 (M + H)⁺amino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide 13.975-Chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2- 1 566.3 (M + H)⁺methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide 13.985-Chloro-2-methylamino-N-[4-(1,2,2,2-tetrafluoro-1- 1 616.3 (M + H)⁺trifluoromethyl-ethyl)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.99N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 1 504.3 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.100N-Butyl-N-(4-tert-butyl-benzyl)-5-chloro-2- 1 388.3 (M + H)⁺methylamino-nicotinamide 13.1015-Chloro-2-cyclopropylamino-N-[2-(3,4-dichloro- 1 642.2 (M + H)⁺phenyl)-ethyl]-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide 13.1025-Chloro-2-cyclopropylamino-N-[2-(4-fluoro-phenyl)- 1 592.3 (M + H)⁺ethyl]-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide 13.103N-(4-tert-Butyl-benzyl)-5-chloro-2-cyclopropylamino- 1 530.3 (M + H)⁺N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.1045-Chloro-N-(4-cyclobutyl-benzyl)-N-[2-(3,4-dichloro- 1 502.2 (M + H)⁺phenyl)-ethyl]-2-methylamino-nicotinamide 13.1055-Chloro-N-(4-cyclopentyl-benzyl)-N-[2-(3,4-dichloro- 1 516.3 (M + H)⁺phenyl)-ethyl]-2-methylamino-nicotinamide 13.1065-Chloro-2-cyclopropylamino-N-[4-(1,2,2,2-tetrafluoro- 1 642.3 (M + H)⁺1-trifluoromethyl-ethyl)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.1075-Chloro-N-(4-cyclobutyl-benzyl)-2-cyclopropylamino- 1 528.1 (M + H)⁺N-[2-(3,4-dichloro-phenyl)-ethyl]-nicotinamide 13.1085-Amino-pyrimidine-4-carboxylic acid (4-tert-butyl- 4 457.4 (M + H)⁺benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.1095-Methylamino-pyrimidine-4-carboxylic acid (4-tert- 3 471.3 (M + H)⁺butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.110N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 1 469.4 (M + H)⁺ethyl]-2-methylamino-benzamide 13.1116-Chloro-3-methylamino-pyridine-2-carboxylic acid [2- 1 615.9 (M + H)⁺(3,4-dichloro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-amide 13.1126-Chloro-3-methylamino-pyridine-2-carboxylic acid [2- 1 566.0 (M + H)⁺(4-fluoro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-amide 13.1136-Chloro-3-methylamino-pyridine-2-carboxylic acid [4- 1 616.0 (M + H)⁺(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide 13.1146-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 504.0 (M + H)⁺tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.1156-Chloro-3-methylamino-pyridine-2-carboxylic acid 1 388.2 (M + H)⁺butyl-(4-tert-butyl-benzyl)-amide 13.1166-Chloro-3-cyclopropylamino-pyridine-2-carboxylic 1 530.0 (M + H)⁺ acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)- ethyl]-amide 13.1176-Chloro-3-cyclopropylamino-pyridine-2-carboxylic 1 642.0 (M + H)⁺ acid[2-(3,4-dichloro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-amide 13.1186-Chloro-3-cyclopropylamino-pyridine-2-carboxylic 1 592.0 (M + H)⁺ acid[2-(4-fluoro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-amide 13.1196-Chloro-3-cyclopropylamino-pyridine-2-carboxylic 1 642.0 (M + H)⁺ acid[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide 13.1206-Chloro-3-methylamino-pyridazine-4-carboxylic acid 1 505.0 (M + H)⁺(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]- amide 13.1215-Fluoro-N-[2-(4-fluoro-phenyl)-ethyl]-2-methylamino- 1 550.2 (M + H)⁺N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)- benzyl]-nicotinamide13.122 N-(4-Cyclobutyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 1 500.1 (M +H)⁺ ethyl]-2-ethylamino-5-fluoro-nicotinamide 13.1236-Chloro-3-methylamino-pyridazine-4-carboxylic acid 1 617.0 (M + H)⁺[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide 13.1246-Chloro-3-methylamino-pyridazine-4-carboxylic acid 1 503.0 (M + H)⁺(4-cyclobutyl-benzyl)-[2-(3-trifluoromethyl-phenyl)- ethyl]-amide 13.1255-Bromo-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methyl- 1 659.8 (M + H)⁺amino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide 13.1265-Bromo-N-(4-cyclobutyl-benzyl)-N-[2-(3,4-dichloro- 1 545.9 (M + H)⁺phenyl)-ethyl]-2-methylamino-nicotinamide 13.1275-Chloro-N-(4-cyclobutyl-benzyl)-2-methylamino-N-[2- 1 502.1 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.1286-Methoxy-3-methylamino-pyridazine-4-carboxylic acid 1 501.1 (M + H)⁺(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]- amide 13.1292-Amino-N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro- 1 456.0 (M + H)⁺phenyl)-ethyl]-nicotinamide 13.1306-Chloro-3-methylamino-pyridazine-4-carboxylic acid 1 616.9 (M + H)⁺[2-(3,4-dichloro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-amide 13.1312-Ethylamino-5-fluoro-N-[2-(4-fluoro-phenyl)-ethyl]- 1 564.4 (M + H)⁺N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)- benzyl]-nicotinamide13.132 3-Methylamino-pyridazine-4-carboxylic acid (4-tert- 1 471.2 (M +H)⁺ butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.133N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 1 484.5 (M + H)⁺ethyl]-5-methyl-2-methylamino-nicotinamide 13.1345-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2- 1 582.1 (M + H)⁺methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide 13.1355-Chloro-N-(4-cyclopropyl-benzyl)-2-methylamino-N- 1 488.3 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.1365-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-(4- 1 454.3 (M + H)⁺cyclopropyl-benzyl)-2-methylamino-nicotinamide 13.137#!(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 1 498.3 (M + H)⁺ethyl]-2-ethylamino-5-methyl-nicotinamide 13.1385-Chloro-N-(4-cyclopropyl-benzyl)-2-ethylamino-N-[2- 1 502.2 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.1396-Chloro-3-methylamino-pyridine-2-carboxylic acid [2- 1 582.1 (M + H)⁺(4-chloro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-amide 13.1406-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 488.3 (M + H)⁺cyclopropyl-benzyl)-[2-(3-trifluoromethyl-phenyl)- ethyl]-amide 13.1416-Chloro-3-methylamino-pyridine-2-carboxylic acid [2- 1 454.3 (M + H)⁺(4-chloro-phenyl)-ethyl]-(4-cyclopropyl-benzyl)-amide 13.142N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 4 546.3 (M + H)⁺ethyl]-2-methylamino-5-phenyl-nicotinamide 13.1433-Amino-6-methyl-pyridine-2-carboxylic acid (4-tert- 1 470.4 (M + H)⁺butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.1443-Amino-6-methyl-pyrazine-2-carboxylic acid (4-tert- 1 471.2 (M + H)⁺butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.1453-Amino-6-chloro-pyrazine-2-carboxylic acid (4-tert- 1 491.2 (M + H)⁺butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.1466-Chloro-3-methylamino-pyrazine-2-carboxylic acid (4- 3 505.3 (M + H)⁺tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.1476-Methyl-3-methylamino-pyrazine-2-carboxylic acid (4- 3 485.4 (M + H)⁺tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.1486-Chloro-3-ethylamino-pyridine-2-carboxylic acid (4- 1 518.2 (M + H)⁺tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.1496-Chloro-3-ethylamino-pyridine-2-carboxylic acid (4- 1 518.3 (M + H)⁺tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.150N-(4-tert-Butyl-benzyl)-2-chloro-N-[2-(3,4-dichloro- 1 504.0 (M + H)⁺phenyl)-ethyl]-5-methylamino-isonicotinamide 13.151N-(4-tert-Butyl-benzyl)-2-chloro-5-methylamino-N-[2- 1 504.3 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-isonicotinamide 13.1526-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 436.3 (M + H)⁺tert-butyl-benzyl)-phenethyl-amide 13.1536-Chloro-3-methylamino-pyridine-2-carboxylic acid [2- 1 573.9 (M + H)⁺(3,4-dichloro-phenyl)-ethyl]-(4-(pentafluorothio)- benzyl)-amide 13.154N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)- 4 496.4 (M + H)⁺ethyl]-2-methylamino-5-vinyl-nicotinamide 13.1552-Chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-5-methyl- 1 616.3 (M + H)⁺amino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-isonicotinamide 13.1565-Amino-2-chloro-pyrimidine-4-carboxylic acid (4-tert- 1 491.2 (M + H)⁺butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide 13.1572-Chloro-5-methylamino-pyrimidine-4-carboxylic acid 3 505.3 (M + H)⁺(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]- amide 13.1585-Chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-N-(4-iso- 1 490.2 (M + H)⁺propyl-benzyl)-2-methylamino-nicotinamide 13.1596-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 502.2 (M + H)⁺cyclobutyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]- amide 13.1606-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 502.3 (M + H)⁺cyclobutyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.1612-Chloro-N-(4-cyclobutyl-benzyl)-N-[2-(3,4-dichloro- 1 502.2 (M + H)⁺phenyl)-ethyl]-5-methylamino-isonicotinamide 13.1622-Chloro-N-(4-cyclobutyl-benzyl)-5-methylamino-N-[2- 1 502.3 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-isonicotinamide 13.1632-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-5- 1 582.2 (M + H)⁺methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-isonicotinamide 13.1642-Chloro-5-methylamino-N-[4-(1,2,2,2-tetrafluoro-1- 1 616.4 (M + H)⁺trifluoromethyl-ethyl)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-isonicotinamide 13.1655-Chloro-N-[4-(1-fluoro-cyclopropyl)-benzyl]-2- 1 506.2 (M + H)⁺methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- nicotinamide 13.1665-Chloro-N-[4-(1-fluoro-cyclopropyl)-benzyl]-2- 1 505.3 (M + H)⁺methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.1675-Chloro-N-(4-isopropyl-benzyl)-2-methylamino-N-[2- 1 489.4 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.1685-Chloro-N-(4-isopropyl-benzyl)-2-methylamino-N-[2- 1 489.4 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.1696-Chloro-3-methylamino-pyrazine-2-carboxylic acid (4- 1 491.3 (M + H)⁺isopropyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.1706-Chloro-3-methylamino-pyrazine-2-carboxylic acid (4- 1 505.3 (M + H)⁺tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.1715-Chloro-2-methylamino-N-(4-methyl-benzyl)-N-[2-(3- 1 461.3 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-benzamide 13.1725-Chloro-N-(4-ethyl-benzyl)-2-methylamino-N-[2-(3- 1 475.3 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-benzamide 13.1735-Chloro-N-(4-ethyl-benzyl)-2-methylamino-N-[2-(3- 1 476.3 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.1746-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 490.3 (M + H)⁺isopropyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.1752-Chloro-N-(4-isopropyl-benzyl)-5-methylamino-N-[2- 1 490.5 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-isonicotinamide 13.1765-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-[4-(1- 1 471.2 (M + H)⁺fluoro-cyclopropyl)-benzyl]-2-methylamino-benzamide 13.1775-Chloro-N-(4-isopropyl-benzyl)-2-methylamino-N-[2- 1 506.2 (M + H)⁺(3-trifluoromethoxy-phenyl)-ethyl]-nicotinamide 13.1785-Chloro-N-(4-isopropyl-benzyl)-2-methylamino-N-[2- 1 505.3 (M + H)⁺(3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.1795-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-(4- 1 456.4 (M + H)⁺isopropyl-benzyl)-2-methylamino-nicotinamide 13.1805-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-(4- 1 455.3 (M + H)⁺isopropyl-benzyl)-2-methylamino-benzamide 13.1816-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 472.3 (M + H)⁺tert-butyl-benzyl)-(2,2-difluoro-2-phenyl-ethyl)-amide 13.182N-(4-tert-Butyl-benzyl)-5-chloro-N-{2-[(4-chloro- 1 499.2 (M + H)⁺phenyl)-methyl-amino]-ethyl}-2-methylamino- nicotinamide 13.183N-(4-tert-Butyl-benzyl)-5-chloro-N-{2-[(4-chloro- 1 498.2 (M + H)⁺phenyl)-methyl-amino]-ethyl}-2-methylamino- benzamide 13.1845-Chloro-2-methylamino-N-(4-pentafluoroethyl- 1 565.3 (M + H)⁺benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.1856-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 566.3 (M + H)⁺pentafluoroethyl-benzyl)-[2-(3-trifluoromethyl-phenyl)- ethyl]-amide13.186 5-Chloro-2-methylamino-N-(4-pentafluoroethyl- 1 581.1 (M + H)⁺benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]- benzamide 13.1876-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 582.0 (M + H)⁺pentafluoroethyl-benzyl)-[2-(3-trifluoromethoxy- phenyl)-ethyl]-amide13.188 5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2- 1 531.2 (M + H)⁺methylamino-N-(4-pentafluoroethyl-benzyl)-benzamide 13.1896-Chloro-3-methylamino-pyridine-2-carboxylic acid [2- 1 532.1 (M + H)⁺(4-chloro-phenyl)-ethyl]-(4-pentafluoroethyl-benzyl)- amide 13.1905-Chloro-N-[2-(3-methoxy-phenyl)-ethyl]-2-methyl- 1 527.2 (M + H)⁺amino-N-(4-pentafluoroethyl-benzyl)-benzamide 13.1916-Chloro-3-methylamino-pyridine-2-carboxylic acid [2- 1 528.2 (M + H)⁺(3-methoxy-phenyl)-ethyl]-(4-pentafluoroethyl-benzyl)- amide 13.1925-Chloro-2-methylamino-N-(4-pentafluoroethyl- 1 511.4 (M + H)⁺benzyl)-N-(2-p-tolyl-ethyl)-benzamide 13.1936-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 512.5 (M + H)⁺pentafluoroethyl-benzyl)-(2-p-tolyl-ethyl)-amide 13.1945-Chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2- 1 515.4 (M + H)⁺methylamino-N-(4-pentafluoroethyl-benzyl)-benzamide 13.1956-Chloro-3-methylamino-pyridine-2-carboxylic acid[2- 1 516.3 (M + H)⁺(4-fluoro-phenyl)-ethyl]-(4-pentafluoroethyl-benzyl)- amide 13.1965-Chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2- 1 516.2 (M + H)⁺methylamino-N-(4-pentafluoroethyl-benzyl)- nicotinamide 13.1975-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2- 1 532.1 (M + H)⁺methylamino-N-(4-pentafluoroethyl-benzyl)- nicotinamide 13.1985-Chloro-2-methylamino-N-(4-pentafluoroethyl- 1 582.0 (M + H)⁺benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]- nicotinamide 13.1995-Chloro-N-[2-(3-methoxy-phenyl)-ethyl]-2- 1 528.2 (M + H)⁺methylamino-N-(4-pentafluoroethyl-benzyl)- nicotinamide 13.2005-Chloro-2-methylamino-N-(4-pentafluoroethyl- 1 512.4 (M + H)⁺benzyl)-N-(2-p-tolyl-ethyl)-nicotinamide 13.201N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro- 1 484.5 (M + H)⁺phenylamino)-ethyl]-2-methylamino-benzamide 13.202N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-(2- 1 485.4 (M + H)⁺naphthalen-2-yl-ethyl)-benzamide 13.2036-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 485.3 (M + H)⁺tert-butyl-benzyl)-[2-(4-chloro-phenylamino)-ethyl]- amide 13.2046-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 486.4 (M + H)⁺tert-butyl-benzyl)-(2-naphthalen-2-yl-ethyl)-amide 13.2055-Chloro-2-methylamino-N-(4-pentafluoroethyl- 1 566.3 (M + H)⁺benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- nicotinamide 13.2062-Chloro-5-methylamino-N-(4-pentafluoroethyl- 1 566.3 (M + H)⁺benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- isonicotinamide 13.2072-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-5- 1 532.2 (M + H)⁺methylamino-N-(4-pentafluoroethyl-benzyl)- isonicotinamide 13.2085-Chloro-2-ethylamino-N-(4-pentafluoroethyl-benzyl)- 1 579.3 (M + H)⁺N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2095-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-ethylamino- 1 545.3 (M + H)⁺N-(4-pentafluoroethyl-benzyl)-benzamide 13.210N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-(2- 1 451.2 (M + H)⁺phenoxy-ethyl)-benzamide 13.2116-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 452.3 (M + H)⁺tert-butyl-benzyl)-(2-phenoxy-ethyl)-amide 13.2126-Chloro-3-methylamino-pyrazine-2-carboxylic acid (4- 1 453.1 (M + H)⁺cyclobutyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amide 13.2136-Chloro-3-methylamino-pyrazine-2-carboxylic acid (4- 1 503.0 (M + H)⁺cyclobutyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.2146-Chloro-3-methylamino-pyrazine-2-carboxylic acid [2- 1 469.2 (M + H)⁺(4-chloro-phenyl)-ethyl]-(4-cyclobutyl-benzyl)-amide 13.2156-Chloro-3-methylamino-pyridine-2-carboxylic acid [2- 1 468.1 (M + H)⁺(4-chloro-phenyl)-ethyl]-(4-cyclobutyl-benzyl)-amide 13.2166-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 452.1 (M + H)⁺cyclobutyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amide 13.2173-Amino-6-methyl-pyridine-2-carboxylic acid [2-(4- 1 434.4 (M + H)⁺chloro-phenyl)-ethyl]-(4-cyclobutyl-benzyl)-amide 13.2183-Amino-6-methyl-pyridine-2-carboxylic acid (4-cyclo- 1 418.3 (M + H)⁺butyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amide 13.2193-Amino-6-methyl-pyridine-2-carboxylic acid (4-cyclo- 1 468.5 (M + H)⁺butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.2206-Methyl-3-methylamino-pyridine-2-carboxylic acid (4- 3 432.4 (M + H)⁺cyclobutyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amide 13.2216-Methyl-3-methylamino-pyridine-2-carboxylic acid (4- 3 482.5 (M + H)⁺cyclobutyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]- amide 13.222N-(4-tert-Butyl-benzyl)-5-chloro-3-fluoro-2- 1 521.4 (M + H)⁺methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.223N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3,4-dichloro- 1 521.3 (M + H)⁺phenyl)-ethyl]-3-fluoro-2-methylamino-benzamide 13.2242-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-3- 1 549.4 (M + H)⁺fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2252-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(4- 1 565.1 (M + H)⁺fluoro-phenyl)-ethyl]-3-iodo-benzamide 13.226N-(4-tert-Butyl-benzyl)-2,3-dichloro-6-methylamino-N- 5 537.5 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2276-Amino-N-(4-tert-butyl-benzyl)-2,3-dichloro-N-[2-(3- 5 522.2 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-benzamide 13.228N-(4-tert-Butyl-benzyl)-2,3-dichloro-6-(cyclopropane- 6 591.5 (M + H)⁺carbonyl-amino)-N-[2-(3-trifluoromethyl-phenyl)- ethyl]-benzamide 13.2296-Acetylamino-N-(4-tert-butyl-benzyl)-2,3-dichloro-N- 6 565.4 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.230N-(4-tert-Butyl-benzyl)-2,3-dichloro-6-propionylamino- 6 579.4 (M + H)⁺N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2316-Amino-N-(4-tert-butyl-benzyl)-2,3-dichloro-N-[2-(3- 1 521.5 (M + H)⁺difluoromethoxy-phenyl)-ethyl]-benzamide 13.2326-Acetylamino-N-(4-tert-butyl-benzyl)-2,3-dichloro-N- 6 580.3 (M + H)⁺[2-(3-difluoromethoxy-phenyl)-ethyl]-benzamide 13.233N-(4-tert-Butyl-benzyl)-2,3-dichloro-N-[2-(3-difluoro- 6 577.3 (M + H)⁺methoxy-phenyl)-ethyl]-6-propionylamino-benzamide 13.2342-Amino-N-(4-tert-butyl-benzyl)-6-chloro-N-[2-(3-tri- 1 489.4 (M + H)⁺fluoromethyl-phenyl)-ethyl]-benzamide 13.2352-Amino-N-(4-tert-butyl-benzyl)-6-methyl-N-[2-(3-tri- 1 469.5 (M + H)⁺fluoromethyl-phenyl)-ethyl]-benzamide 13.2362-Acetylamino-N-(4-tert-butyl-benzyl)-6-chloro-N-[2- 6 531.3 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2372-Acetylamino-N-(4-tert-butyl-benzyl)-6-methyl-N-[2- 6 511.5 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2382-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-tri- 1 505.1 (M + H)⁺fluoromethoxy-phenyl)-ethyl]-benzamide 13.2392-Acetylamino-N-butyl-N-(4-tert-butyl-benzyl)-5- 6 415.3 (M + H)⁺chloro-benzamide 13.2402-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2- 6 547.3 (M + H)⁺(3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.2416-Amino-N-(4-tert-butyl-benzyl)-3-chloro-2-fluoro-N- 1 507.1 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2422-Amino-N-(4-tert-butyl-benzyl)-3-chloro-6-fluoro-N- 1 507.3 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.243N-(4-tert-Butyl-benzyl)-2,3-dichloro-6-(2,2,2-trifluoro- 6 619.3 (M +H)⁺ acetylamino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide13.244 6-Acetylamino-N-(4-tert-butyl-benzyl)-3-chloro-2- 6 549.4 (M +H)⁺ fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2452-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(2- 1 455.4 (M + H)⁺chloro-phenyl)-ethyl]-benzamide 13.2462-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3- 1 455.4 (M + H)⁺chloro-phenyl)-ethyl]-benzamide 13.2472-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2- 6 496.2 (M + H)⁺(2-chloro-phenyl)-ethyl]-benzamide 13.2482-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2- 6 496.2 (M + H)⁺(3-chloro-phenyl)-ethyl]-benzamide 13.2492-Acetylamino-N-(4-tert-butyl-benzyl)-3-chloro-6- 6 549.4 (M + H)⁺fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2502-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(4- 1 455.4 (M + H)⁺chloro-phenyl)-ethyl]-benzamide 13.2512-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(4- 1 451.2 (M + H)⁺methoxy-phenyl)-ethyl]-benzamide 13.2522-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2- 6 497.1 (M + H)⁺(4-chloro-phenyl)-ethyl]-benzamide 13.2532-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2- 6 493.2 (M + H)⁺(4-methoxy-phenyl)-ethyl]-benzamide 13.254N-(4-tert-Butyl-benzyl)-3-chloro-6-fluoro-2- 3 521.4 (M + H)⁺methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2552-Amino-N-(4-tert-butyl-benzyl)-3,5-dichloro-6-fluoro- 1 541.3 (M + H)⁺N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2562-Acetylamino-5-chloro-N-[(R)-2-(4-chloro-phenyl)-2- 6 497 (M + H)⁺hydroxy-ethyl]-N-(4-cyclopropyl-benzyl)-benzamide 13.2572-Acetylamino-N-(4-tert-butyl-benzyl)-3,5-dichloro-6- 6 583 (M + H)⁺fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2582-Amino-3,5-dichloro-N-[(R)-2-(4-chloro-phenyl)-2- 6 507.2 (M + H)⁺hydroxy-ethyl]-N-(4-cyclopropyl-benzyl)-6-fluoro-benz- amide 13.2596-Acetylamino-2,3-dichloro-N-[(R)-2-(4-chloro- 6 531.2 (M + H)⁺phenyl)-2-hydroxy-ethyl]-N-(4-cyclopropyl-benzyl)- benzamide 13.2602-Acetylamino-3,5-dichloro-N-[(R)-2-(4-chloro- 6 549.3 (M + H)⁺phenyl)-2-hydroxy-ethyl]-N-(4-cyclopropyl-benzyl)-6- fluoro-benzamide13.261 2-Acetylamino-5-chloro-N-(4-cyclopropyl-benzyl)-N- 6 531.3 (M +H)⁺ [2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.2622-Acetylamino-5-chloro-N-(4-cyclopropyl-benzyl)-N- 6 515.3 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2632-Amino-3,5-dichloro-N-(4-cyclopropyl-benzyl)-6- 1 541.3 (M + H)⁺fluoro-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]- benzamide 13.2642-Amino-3,5-dichloro-N-(4-cyclopropyl-benzyl)-6- 1 525.3 (M + H)⁺fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2656-Acetylamino-2,3-dichloro-N-(4-cyclopropyl-benzyl)- 6 565.3 (M + H)⁺N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.2666-Acetylamino-2,3-dichloro-N-(4-cyclopropyl-benzyl)- 6 549.2 (M + H)⁺N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2672-Amino-3,5-dichloro-N-(2-chloro-4-cyclopropyl- 1 559.1 (M + H)⁺benzyl)-6-fluoro-N-[2-(3-trifluoromethyl-phenyl)- ethyl]-benzamide13.268 2-Acetylamino-3,5-dichloro-N-(2-chloro-4-cyclopropyl- 1 601.0(M + H)⁺ benzyl)-6-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2692-Acetylamino-3,5-dichloro-N-(4-cyclopropyl-benzyl)- 6 583 (M + H)⁺6-fluoro-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]- benzamide 13.2702-Acetylamino-3,5-dichloro-N-(4-cyclopropyl-benzyl)- 6 567.2 (M + H)⁺6-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2712-Amino-5-chloro-N-(2-chloro-4-cyclopropyl-benzyl)- 1 507.2 (M + H)⁺N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2722-Acetylamino-5-chloro-N-(2-chloro-4-cyclopropyl- 6 547.2 (M + H)⁺benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2735-Chloro-N-(4-cyclopropyl-benzyl)-2-methylamino-N- 7 587.2 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2745-Chloro-2-(cyanomethyl-amino)-N-(4-cyclopropyl- 7 528.1 (M + H)⁺benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]- benzamide 13.2755-Chloro-2-(cyanomethyl-amino)-N-(4-cyclopropyl- 7 511.3 (M + H)⁺benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2762,3-Dichloro-6-(cyanomethyl-amino)-N-(4-cyclopropyl- 7 579.1 (M + H)⁺benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]- benzamide 13.2772,3-Dichloro-N-(4-cyclopropyl-benzyl)-6-methylamino- 7 537.2 (M + H)⁺N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.2782,3-Dichloro-6-(cyanomethyl-amino)-N-(4-cyclopropyl- 7 563.3 (M + H)⁺benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2792,3-Dichloro-N-(4-cyclopropyl-benzyl)-6-methylamino- 7 521.2 (M + H)⁺N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2805-Chloro-N-(4-cyclopropyl-benzyl)-2-ethylamino-N-[2- 1 501.1 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.2815-Chloro-N-(4-cyclopropyl-benzyl)-2-ethylamino-N-[2- 1 517.2 (M + H)⁺(3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.282N-(4-tert-Butyl-benzyl)-5-chloro-2-ethylamino-N-[2-(3- 1 533.2 (M + H)⁺trifluoromethoxy-phenyl)-ethyl]-benzamide 13.2835-Chloro-N-(4-cyclopropyl-2-fluoro-benzyl)-2-ethyl- 1 519.1 (M + H)⁺amino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2845-Chloro-N-(4-cyclopropyl-3-fluoro-benzyl)-2-ethyl- 1 519.1 (M + H)⁺amino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2853,5-Dichloro-N-(4-cyclopropyl-benzyl)-2-fluoro-6- 7 539.2 (M + H)⁺methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.2862-Acetylamino-3,5-dichloro-N-(4-cyclopropyl-benzyl)- 6 565.2 (M + H)⁺N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.2873,5-Dichloro-N-(4-cyclopropyl-benzyl)-2-methylamino- 7 537.2 (M + H)⁺N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.2883,5-Dichloro-N-(4-cyclopropyl-benzyl)-2-ethylamino-N- 7 550.1 (M + H)⁺[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.2893,5-Dichloro-2-(cyanomethyl-amino)-N-(4-cyclopropyl- 7 562.3 (M + H)⁺benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]- benzamide 13.2903,5-Dichloro-2-(cyanomethyl-amino)-N-(4-cyclopropyl- 7 564.2 (M + H)⁺benzyl)-6-fluoro-N-[2-(3-trifluoromethyl-phenyl)- ethyl]-benzamide13.291 5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-(4- 7 452.9 (M + H)⁺cyclopropyl-benzyl)-2-methylamino-benzamide 13.2925-Chloro-N-(4-cyclopropyl-benzyl)-N-[2-(4-fluoro- 7 437 (M + H)⁺phenyl)-ethyl]-2-methylamino-benzamide 13.293(2-{(4-tert-Butyl-benzyl)-[2-(3-trifluoromethoxy- 7 591.2 (M + H)⁺phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)- acetic acid ethyl ester13.294 5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-(4- 7 467.4 (M + H)⁺cyclopropyl-benzyl)-2-ethylamino-benzamide 13.2955-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2- 7 478.4 (M + H)⁺(cyanomethyl-amino)-N-(4-cyclopropyl-benzyl)- benzamide 13.2965-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2- 7 581.1 (M + H)⁺methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide 13.297N-(4-tert-Butyl-benzyl)-5-chloro-2-(cyanomethyl- 7 544.3 (M + H)⁺amino)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]- benzamide 13.298N-(4-tert-Butyl-benzyl)-5-chloro-2-(cyanomethyl- 7 519.4 (M + H)⁺amino)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]- benzamide 13.2995-Chloro-2-methylamino-N-(4-trifluoromethoxy- 7 531.1 (M + H)⁺benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.3005-Chloro-2-ethylamino-N-(4-trifluoromethoxy-benzyl)- 7 545.2 (M + H)⁺N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.3015-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-ethylamino- 7 595.1 (M + H)⁺N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)- benzyl]-benzamide13.302 5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2- 7 606.4 (M + H)⁺(cyanomethyl-amino)-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide 13.3035-Chloro-2-(cyanomethyl-amino)-N-(4- 7 556.0 (M + H)⁺trifluoromethoxy-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.3045-Chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2- 7 481.2 (M + H)⁺methylamino-N-(4-trifluoromethoxy-benzyl)-benzamide 13.3055-Chloro-2-ethylamino-N-[2-(4-fluoro-phenyl)-ethyl]- 7 495.2 (M + H)⁺N-(4-trifluoromethoxy-benzyl)-benzamide 13.3065-Chloro-2-(cyanomethyl-amino)-N-[2-(4-fluoro- 7 506.1 (M + H)⁺phenyl)-ethyl]-N-(4-trifluoromethoxy-benzyl)- benzamide 13.307{4-Chloro-2-[[2-(4-fluoro-phenyl)-ethyl]-(4-trifluoromethoxy- 7 553.0(M + H)⁺ benzyl)-carbamoyl]-phenylamino}-acetic acid ethyl ester 13.308{4-Chloro-2-[[2-(4-fluoro-phenyl)-ethyl]-(4- 8 525 (M + H)⁺trifluoromethoxy-benzyl)-carbamoyl]-phenylamino}- acetic acid 13.3095-Chloro-N-(3-chloro-4-trifluoromethoxy-benzyl)-N- 7 515.0 (M + H)⁺[2-(4-fluoro-phenyl)-ethyl]-2-methylamino-benzamide 13.3105-Chloro-2-(cyanomethyl-amino)-N-(4-cyclobutyl- 7 525.2 (M + H)⁺benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.3115-Chloro-N-(3-chloro-4-trifluoromethoxy-benzyl)-2- 7 529.1 (M + H)⁺ethylamino-N-[2-(4-fluoro-phenyl)-ethyl]-benzamide 13.3125-Chloro-N-(3-chloro-4-trifluoromethoxy-benzyl)-2- 7 541.1 (M + H)⁺(cyanomethyl-amino)-N-[2-(4-fluoro-phenyl)-ethyl]- benzamide 13.3135-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2- 7 497 (M + H)⁺methylamino-N-(4-trifluoromethoxy-benzyl)-benzamide 13.3145-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-ethylamino- 7 511.2 (M + H)⁺N-(4-trifluoromethoxy-benzyl)-benzamide 13.3155-Chloro-N-(4-cyclobutyl-benzyl)-2-methylamino-N-[2- 7 501.1 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.3165-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2- 7 522.0 (M + H)⁺(cyanomethyl-amino)-N-(4-trifluoromethoxy-benzyl)- benzamide 13.3175-Chloro-N-[4-(1-methoxy-cyclopropyl)-benzyl]-2- 7 533.2 (M + H)⁺methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]- benzamide 13.3185-Chloro-2-ethylamino-N-[4-(1-methoxy-cyclopropyl)- 7 547.3 (M + H)⁺benzyl]-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benz- amide 13.3195-Chloro-2-(cyanomethyl-amino)-N-[4-(1-methoxy- 7 558.2 (M + H)⁺cyclopropyl)-benzyl]-N-[2-(3-trifluoromethoxy-phenyl)- ethyl]-benzamide13.320 5-Chloro-N-(4-cyclobutyl-benzyl)-2-methylamino-N-[2- 7 517.2 (M +H)⁺ (3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.3215-Chloro-N-(4-cyclobutyl-benzyl)-2-ethylamino-N-[2- 7 530.2 (M + H)⁺(3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.3225-Chloro-2-(cyanomethyl-amino)-N-(4-cyclobutyl- 7 541.1 (M + H)⁺benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]- benzamide 13.323N-(4-Benzyloxy-benzyl)-5-chloro-2-methylamino-N-[2- 1 553.1 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.324[4-({(5-Chloro-2-methylamino-benzoyl)-[2-(3-trifluoro- 9 535.0 (M + H)⁺methyl-phenyl)-ethyl]-amino}-methyl)-phenoxy]-acetic acid methyl ester13.325 N-(4-tert-Butyl-benzyl)-2,3-dichloro-N-[2-(4-chloro- 1 503.0 (M +H)⁺ phenyl)-ethyl]-6-methylamino-benzamide 13.3262,3-Dichloro-N-[2-(4-chloro-phenyl)-ethyl]-6-methyl- 1 615.2 (M + H)⁺amino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide 13.327N-(4-tert-Butyl-benzyl)-2,3-dichloro-6-methylamino-N- 1 553.4 (M + H)⁺[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.328N-(4-tert-Butyl-benzyl)-2,3-dichloro-N-[2-(4-fluoro- 1 487.3 (M + H)⁺phenyl)-ethyl]-6-methylamino-benzamide 13.3295-Chloro-N-[4-(4-cyano-benzyloxy)-benzyl]-2-methyl- 9 578.2 (M + H)⁺amino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.3305-Chloro-N-[4-(4-fluoro-benzyloxy)-benzyl]-2-methyl- 9 571.2 (M + H)⁺amino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.3312,3-Dichloro-N-[4-(1-methoxy-cyclopropyl)-benzyl]-6- 1 551.1 (M + H)⁺methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.3325-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-[4-(1-meth- 1 483.2 (M + H)⁺oxy-cyclopropyl)-benzyl]-2-methylamino-benzamide 13.3332,3-Dichloro-N-[2-(4-chloro-phenyl)-ethyl]-N-[4-(1- 1 517.1 (M + H)⁺methoxy-cyclopropyl)-benzyl]-6-methylamino- benzamide 13.3346-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 519.3 (M + H)⁺tert-butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)- ethyl]-amide 13.335N-(4-tert-Butoxy-benzyl)-2,3-dichloro-N-[2-(4-chloro- 1 519.2 (M + H)⁺phenyl)-ethyl]-6-methylamino-benzamide 13.336N-(4-tert-Butoxy-benzyl)-5-chloro-N-[2-(4-chloro- 1 485.2 (M + H)⁺phenyl)-ethyl]-2-methylamino-benzamide 13.3375-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2- 1 481.0 (M + H)⁺methylamino-N-(4-trifluoromethyl-benzyl)-benzamide 13.3382,3-Dichloro-N-[2-(4-chloro-phenyl)-ethyl]-6-methyl- 1 515.0 (M + H)⁺amino-N-(4-trifluoromethyl-benzyl)-benzamide 13.3395-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2- 1 529.0 (M + H)⁺methylamino-N-[4-(1,1,2,2-tetrafluoro-ethoxy)-benzyl]- benzamide 13.3405-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2- 1 505.2 (M + H)⁺methylamino-N-(4-phenoxy-benzyl)-benzamide 13.3412,3-Dichloro-N-[2-(4-chloro-phenyl)-ethyl]-6-methyl- 1 563.3 (M + H)⁺amino-N-[4-(1,1,2,2-tetrafluoro-ethoxy)-benzyl]-benzamide 13.3422,3-Dichloro-N-[2-(4-chloro-phenyl)-ethyl]-6-methyl- 1 541.3 (M + H)⁺amino-N-(4-phenoxy-benzyl)-benzamide 13.3435-Chloro-2-methylamino-N-[4-(3,3,3-trifluoro-2- 9 575.3 (M + H)⁺hydroxy-propoxy)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.344 Methanesulfonic acid4-({(5-chloro-2-methylamino- 9 541.1 (M + H)⁺benzoyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amino}- methyl)-phenylester 13.345 N-(4-tert-Butoxy-benzyl)-5-chloro-N-[2-(4-chloro- 1 499.3(M + H)⁺ phenyl)-ethyl]-2-ethylamino-benzamide 13.346N-(4-tert-Butoxy-benzyl)-5-chloro-N-[2-(4-chloro- 1 486.2 (M + H)⁺phenyl)-ethyl]-2-methylamino-nicotinamide 13.3476-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 486.2 (M + H)⁺tert-butoxy-benzyl)-[2-(4-chloro-phenyl)-ethyl]-amide 13.348N-(4-tert-Butoxy-benzyl)-5-chloro-2-methylamino-N- 1 519.2 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.3496-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 520.3 (M + H)⁺tert-butoxy-benzyl)-[2-(3-trifluoromethyl-phenyl)- ethyl]-amide 13.350N-(4-tert-Butoxy-benzyl)-5-chloro-2-methylamino-N- 1 520.3 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide 13.3515-Chloro-N-(4-cyclopropylmethoxy-benzyl)-2-methyl- 9 517.2 (M + H)⁺amino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.352N-(4-tert-Butoxy-benzyl)-5-chloro-2-methylamino-N- 1 535.4 (M + H)⁺[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide 13.3536-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 536.3 (M + H)⁺tert-butoxy-benzyl)-[2-(3-trifluoromethoxy-phenyl)- ethyl]-amide 13.354N-(4-tert-Butoxy-benzyl)-5-chloro-N-[2-(4-fluoro- 1 469.2 (M + H)⁺phenyl)-ethyl]-2-methylamino-benzamide 13.3556-Chloro-3-methylamino-pyridine-2-carboxylic acid (4- 1 470.2 (M + H)⁺tert-butoxy-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amide 13.356N-(4-tert-Butoxy-benzyl)-5-chloro-N-[2-(4-fluoro- 1 470.2 (M + H)⁺phenyl)-ethyl]-2-methylamino-nicotinamide 13.357N-(4-tert-Butoxy-benzyl)-5-chloro-2-methylamino-N- 1 536.4 (M + H)⁺[2-(3-trifluoromethoxy-phenyl)-ethyl]-nicotinamide 13.358N-(4-tert-Butyl-benzyl)-5-chloro-2-ethylamino-N-[2-(4- 1 466.0 (M + H)⁺fluoro-phenyl)-ethyl]-benzamide 13.359N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro- 1 482 (M + H)⁺phenyl)-ethyl]-2-ethylamino-benzamide 13.3602-Amino-N-(4-tert-butyl-benzyl)-3,5-dichloro-N-[2-(3- 1 523.2 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-benzamide 13.3612-Amino-N-(4-tert-butyl-benzyl)-3,5-dimethyl-N-[2-(3- 1 483.4 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-benzamide 13.3622-Amino-3,5-dibromo-N-(4-tert-butyl-benzyl)-N-[2-(3- 1 613.2 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-benzamide 13.3632-Amino-N-(4-tert-butyl-benzyl)-5-methyl-N-[2-(3-tri- 1 469.2 (M + H)⁺fluoromethyl-phenyl)-ethyl]-benzamide 13.364N-(4-tert-Butyl-benzyl)-2-methylamino-N-[2-(3- 1 469.2 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-benzamide 13.3652-Amino-N-(4-tert-butyl-benzyl)-5-iodo-N-[2-(3-tri- 1 581.1 (M + H)⁺fluoromethyl-phenyl)-ethyl]-benzamide 13.3662-Amino-5-bromo-N-(4-tert-butyl-benzyl)-N-[2-(3-tri- 1 535.3 (M + H)⁺fluoromethyl-phenyl)-ethyl]-benzamide 13.3673,5-Dibromo-N-(4-tert-butyl-benzyl)-2-methylamino- 11 627.2 (M + H)⁺N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.3682-Amino-3-bromo-N-(4-tert-butyl-benzyl)-5-iodo-N- 11 661.0 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.3692-Amino-5-bromo-N-(4-tert-butyl-benzyl)-3-chloro-N- 12 569.1 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.3702-Amino-N-(4-tert-butyl-benzyl)-3-chloro-5-iodo-N-[2- 12 615.3 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.371N-(4-tert-Butyl-benzyl)-N-[2-(3-fluoro-4- 1 487.4 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-2-methylamino- benzamide 13.372N-(4-tert-Butyl-benzyl)-N-[2-(2-fluoro-3- 1 487.4 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-2-methylamino- benzamide 13.373N-(4-tert-Butyl-benzyl)-N-[2-(3-chloro-2-fluoro- 1 453.3 (M + H)⁺phenyl)-ethyl]-2-methylamino-benzamide 13.374N-(4-tert-Butyl-benzyl)-N-[2-(3-chloro-4-fluoro- 1 453.3 (M + H)⁺phenyl)-ethyl]-2-methylamino-benzamide 13.375N-(4-tert-Butyl-benzyl)-N-[2-(3-difluoromethoxy- 1 467.4 (M + H)⁺phenyl)-ethyl]-2-methylamino-benzamide 13.376N-(4-tert-Butyl-benzyl)-N-[2-(4-chloro-phenyl)-ethyl]- 1 435.3 (M + H)⁺2-methylamino-benzamide 13.377N-(4-tert-Butyl-benzyl)-N-[2-(4-chloro-3-fluoro- 1 453.4 (M + H)⁺phenyl)-ethyl]-2-methylamino-benzamide 13.378N-(4-tert-Butyl-benzyl)-2-methylamino-N-[2-(3 1 485.5 (M + H)⁺trifluoromethoxy-phenyl)-ethyl]-benzamide 13.379N-(4-tert-Butyl-benzyl)-5-chloro-2-ethylamino-N-[2-(3 5 517.5 (M + H)⁺trifluoromethyl-phenyl)-ethyl]-benzamide 13.380N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2- 5 503.5 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.3812-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-tri- 1 489.4 (M + H)⁺fluoromethyl-phenyl)-ethyl]-benzamide 13.382N-(4-tert-Butyl-benzyl)-2-(cyanomethyl-amino)-N-[2- 1 494.5 (M + H)⁺(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.383N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3-chloro-4- 5 487.3 (M + H)⁺fluoro-phenyl)-ethyl]-2-methylamino-benzamide 13.384N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3,4-dichloro- 5 505.3 (M + H)⁺phenyl)-ethyl]-2-methylamino-benzamide 13.385N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3-difluorometh- 5 501.2 (M + H)⁺oxy-phenyl)-ethyl]-2-methylamino-benzamide 13.386N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro- 5 469.4 (M + H)⁺phenyl)-ethyl]-2-methylamino-benzamide 13.387N-(4-tert-Butyl-benzyl)-5-chloro-2-(cyclopropylmethyl- 5 **amino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.388(2-{(4-tert-Butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)- 6 545.3 (M −H)⁺ ethyl]-carbamoyl}-4-chloro-phenyl)-carbamic acid methyl ester 13.389N-(4-tert-Butyl-benzyl)-5-chloro-2-isopropylamino-N- 1 531.3 (M + H)⁺[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide 13.390N-(4-tert-Butyl-benzyl)-3-chloro-2-fluoro-6- 1 521.4 (M + H)⁺methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide 13.3912-Amino-5-chloro-N-[2-(3-trifluoromethyl-phenyl)- 1 505.3 (M + H)⁺ethyl]-N-(4-trimethylsilanyl-benzyl)-benzamide 13.3922-Amino-5-chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-(4- 1 471.2 (M + H)⁺trimethylsilanyl-benzyl)-benzamide 13.3932-Amino-5-chloro-N-[2-(4-fluoro-phenyl)-ethyl]-N-(4- 1 455.4 (M + H)⁺trimethylsilanyl-benzyl)-benzamide 13.3942-Amino-5-chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]- 1 507.4 (M + H)⁺N-(4-trimethylsilanyl-benzyl)-benzamide 13.395N-Butyl-N-(4-tert-butyl-benzyl)-2-methylamino-benz 1 353.5 (M + H)⁺amide 13.396 N-(4-tert-Butyl-benzyl)-2,3-dichloro-6- 6 599.1 (M − H)⁻methanesulfonylamino-N-[2-(3-trifluoromethyl- phenyl)-ethyl]-benzamide13.397 N-(4-tert-Butyl-benzyl)-5-chloro-2-methanesulfonyl- 6 529.2 (M +H)⁺ amino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]- benzamide *: Preparedin analogy to example **: ¹H-NMR (CDCl₃, 300 MHz): 0.24(q, 2H), 0.53(q,2H), 0.87(q, 1H), 1.31(s, 9H), 2.91(m, 4H), 3.56(br s, 2H), 4.50(br s,2H), 6.57(d, 1H), 6.95(d, 1H), 6.96-7.18(m, 2H), 7.26-7.50(6H, m).

The compounds of formula I are cholesteryl ester transfer protein (CETP)inhibitors. Atherosclerosis and its associated coronary heart disease isthe leading cause of death in the industrialized world. Risk fordevelopment of coronary heart disease has been shown to be stronglycorrelated with certain plasma lipid levels. Lipids are transported inthe blood by lipoproteins. The general structure of lipoproteins is acore of neutral lipids (triglyceride and cholesterol ester) and anenvelope of polar lipids (phospholipids and non esterified cholesterol).There are three different classes of plasma lipoproteins with differentcore lipid content: the low density lipoprotein (LDL) which ischolesteryl ester (CE) rich; high density lipoprotein (HDL) which isalso cholesteryl ester (CE) rich; and the very low density lipoprotein(VLDL) which is triglyceride (TG) rich. The different lipoproteins canbe separated based on their different flotation density or size.

High LDL-cholesterol (LDL-C) and triglyceride levels are positivelycorrelated, while high levels of HDL-cholesterol (HDL-C) are negativelycorrelated with the risk for developing cardiovascular diseases.

Plasma lipoprotein metabolism can be described as a flux of cholesterolbetween liver and the other tissues. The LDL pathway corresponds to thesecretion of VLDL from the liver to deliver cholesterol by LDL totissues. Any alteration in LDL catabolism could lead to uptake of excesscholesterol in the vessel wall forming foam cells and atherosclerosis.The opposite pathway is the mobilization of free cholesterol fromperipheral tissues by HDL to deliver cholesterol to the liver to beeventually excreted with bile. In humans a significant part ofcholesteryl ester (CE) is transferred from HDL to the VLDL, LDL pathway.This transfer is mediated by a 70,000 dalton plasma glycoprotein, thecholesteryl ester transfer protein (CETP).

Mutations in the CETP gene associated with CETP deficiency arecharacterized by high HDL-cholesterol levels (>60 mg/dL) and reducedcardiovascular risk. Such findings are consistent with studies ofpharmacologically mediated inhibition of CETP in the rabbit, which arguestrongly in favor of CETP inhibition as a valid therapeutic approach [LeGoff et al., Pharmacology & Therapeutics 101:17-38 (2004); Okamoto etal., Nature 406:203-207 2000)].

No wholly satisfactory HDL-elevating therapies exist. Niacin cansignificantly increase HDL, but has serious toleration issues whichreduce compliance. Fibrates and the HMG CoA reductase inhibitors raiseHDL-cholesterol only modestly (−10-12%). As a result, there is asignificant unmet medical need for a well tolerated agent which cansignificantly elevate plasma HDL levels. The net result of CETP activityis a lowering of HDL-C and an increase in LDL-C. This effect onlipoprotein profile is believed to be pro-atherogenic, especially insubjects whose lipid profile constitutes an increased risk for coronaryheart disease. Therefore by inhibiting CETP activity there is thepotential to inverse this relationship towards a lower risk andultimately to protect against coronary heart diseases and associatedmortality.

Thus, CETP inhibitors are useful as medicaments for the treatment and/orprophylaxis of atherosclerosis, peripheral vascular disease,dyslipidemia, hyperbeta-lipoproteinemia, hypoalphalipoproteinemia,hypercholesterolemia, hypertriglyceridemia, familialhypercholesterolemia, cardiovascular disorders, angina, ischemia,cardiac ischemia, stroke, myocardial infarction, reperfusion injury,angioplastic restenosis, hypertension, and vascular complications ofdiabetes, obesity or endotoxemia.

In addition, CETP inhibitors may be used in combination with anothercompound, said compound being an HMG-CoA reductase inhibitor, amicrosomal triglyceride transfer protein (MTP)/ApoB secretion inhibitor,a PPAR activator, a bile acid reuptake inhibitor, a cholesterolabsorption inhibitor, a cholesterol synthesis inhibitor, a fibrate,niacin, an ion-exchange resin, an antioxidant, an ACAT inhibitor or abile acid sequestrant.

As described above, the compounds of formula I of the present inventioncan be used as medicaments for the treatment and/or prophylaxis ofdiseases which are mediated by CETP. Examples of such diseases areatherosclerosis, peripheral vascular disease, dyslipidemia,hyperbetalipoproteinemia, hypoalphalipoproteinemia,hypercholesterolemia, hypertriglyceridemia, familialhypercholesterolemia, cardiovascular disorders, angina, ischemia,cardiac ischemia, stroke, myocardial infarction, reperfusion injury,angioplastic restenosis, hypertension, and vascular complications ofdiabetes, obesity or endotoxemia. The use as medicament for thetreatment and/or prevention of dyslipidemia is preferred.

The invention therefore also relates to pharmaceutical compositionscomprising a compound as defined above and a pharmaceutically acceptablecarrier and/or adjuvant.

Further, the invention relates to compounds as defined above for use astherapeutically active substances, particularly as therapeutic activesubstances for the treatment and/or prophylaxis of diseases which aremediated by CETP. Examples of such diseases are atherosclerosis,peripheral vascular disease, dyslipidemia, hyperbetalipoproteinemia,hypoalphalipoproteinemia, hypercholesterolemia, hypertriglyceridemia,familial hypercholesterolemia, cardiovascular disorders, angina,ischemia, cardiac ischemia, stroke, myocardial infarction, reperfusioninjury, angioplastic restenosis, hypertension, and vascularcomplications of diabetes, obesity or endotoxemia.

In another embodiment, the invention relates to a method for thetreatment and/or prophylaxis of diseases which are mediated by CETP.Examples of such diseases are atherosclerosis, peripheral vasculardisease, dyslipidemia, hyperbetalipoproteinemia,hypoalphalipoproteinemia, hypercholesterolemia, hypertriglyceridemia,familial hypercholesterolemia, cardiovascular disorders, angina,ischemia, cardiac ischemia, stroke, myocardial infarction, reperfusioninjury, angioplastic restenosis, hypertension, and vascularcomplications of diabetes, obesity or endotoxemia. A method for thetreatment and/or prophylaxis of dyslipidemia is preferred.

The invention further relates to the use of compounds of formula I asdefined above for the treatment and/or prophylaxis of diseases aremediated by CETP. Examples of such diseases are atherosclerosis,peripheral vascular disease, dyslipidemia, hyperbetalipoproteinemia,hypoalphalipoproteinemia, hypercholesterolemia, hypertriglyceridemia,familial hypercholesterolemia, cardiovascular disorders, angina,ischemia, cardiac ischemia, stroke, myocardial infarction, reperfusioninjury, angioplastic restenosis, hypertension, and vascularcomplications of diabetes, obesity or endotoxemia. The use of compoundsof formula I as defined above for the treatment and/or prophylaxis ofdyslipidemia is preferred.

In addition, the invention relates to the use of compounds of formula Ias defined above for the preparation of medicaments for the treatmentand/or prophylaxis of diseases are mediated by CETP. Examples of suchdiseases are atherosclerosis, peripheral vascular disease, dyslipidemia,hyperbetalipoproteinemia, hypoalphalipoproteinemia,hypercholesterolemia, hypertriglyceridemia, familialhypercholesterolemia, cardiovascular disorders, angina, ischemia,cardiac ischemia, stroke, myocardial infarction, reperfusion injury,angioplastic restenosis, hypertension, and vascular complications ofdiabetes, obesity or endotoxemia. The use of compounds of formula I asdefined above for the preparation of medicaments for the treatmentand/or prophylaxis of dyslipidemia is preferred.

In addition, CETP inhibitors are useful in combination with anothercompound, said compound being an HMG-CoA reductase inhibitor, anmicrosomal triglyceride transfer protein (MTP)/ApoB secretion inhibitor,a PPAR activator, a bile acid reuptake inhibitor, a cholesterolabsorption inhibitor, a cholesterol synthesis inhibitor, a fibrate,niacin, an ion-exchange resin, an antioxidant, an ACAT inhibitor or abile acid sequestrant.

The invention therefore also relates to pharmaceutical compositionscomprising a compound of formula I as defined above in combination withan HMG-CoA reductase inhibitor, an microsomal triglyceride transferprotein (MTP)/ApoB secretion inhibitor, a PPAR activator, a bile acidreuptake inhibitor, a cholesterol absorption inhibitor, a cholesterolsynthesis inhibitor, a fibrate, niacin, an ion-exchange resin, anantioxidant, an ACAT inhibitor or a bile acid sequestrant, as well as apharmaceutically acceptable carrier and/or adjuvant.

The invention further relates to the use of compounds of formula I asdefined above in combination with an HMG-CoA reductase inhibitor, amicrosomal triglyceride transfer protein (MTP)/ApoB secretion inhibitor,a PPAR activator, a bile acid reuptake inhibitor, a cholesterolabsorption inhibitor, a cholesterol synthesis inhibitor, a fibrate,niacin, an ion-exchange resin, an antioxidant, an ACAT inhibitor or abile acid sequestrant for the treatment and/or prophylaxis of diseasessuch as atherosclerosis, peripheral vascular disease, dyslipidemia,hyperbetalipoproteinemia, hypoalphalipoproteinemia,hypercholesterolemia, hypertriglyceridemia, familialhypercholesterolemia, cardiovascular disorders, angina, ischemia,cardiac ischemia, stroke, myocardial infarction, reperfusion injury,angioplastic restenosis, hypertension, and vascular complications ofdiabetes, obesity or endotoxemia, as well as to the use of such acombination for the preparation of corresponding medicaments.

The compounds of formula I and their pharmaceutically acceptable saltspossess valuable pharmacological properties. Specifically, it has beenfound that the compounds of the present invention are inhibitors of thecholesteryl ester transfer protein (CETP).

The following tests were carried out in order to determine the activityof the compounds of formula I.

Activity of CETP inhibitors was determined using a buffer assay system.Partially purified CETP transferred radiolabeled cholesteryl ester fromHDL donor particles to biotin-labeled LDL acceptor particles. Thereaction was stopped by addition of streptavidin-coupled scintillationproximity assay (SPA) beads. These beads captured the biotinylatedacceptor particles and transferred radioactivity was measured. The assaysystem was purchased and performed according to manufacturer'srecommendations (Amersham Biosciences). Inhibitory activity of compoundswas determined as percentage of positive control activity containingCETP together with donor and acceptor particles. Serial dilution ofcompounds was performed in order to determine the IC₅₀ values.

Activity of the compounds was subsequently measured in the presence ofplasma using the same assay as described above except that the source ofCETP was human lipoprotein-deprived serum (LPDS). Inhibitory activity ofcompounds was determined as percentage of positive control activitycontaining all the assay components except compound. Serial dilution ofcompounds was performed in order to determine the IC₅₀ values.

Under the latter assay conditions, the compounds of the presentinvention exhibit IC₅₀ values within the range of about 1 nM to about100 μM, e.g., of about 1 nM to about 1 μM, e.g., of about 1 nM to about200 nM. The following table shows measured values for some selectedcompounds of the present invention.

IC₅₀ (nM) Compound 13.230 5610 Compound 13.63 30010 Compound 13.254 295

In vivo activity of the compounds of formula I were determined inhamster using the following protocol:

Male golden Syrian hamsters (6-week-old, 100-130 g) under standard chowdiet received compounds in the morning by oral gavage using appropriatevehicle, blood was taken 2 h later by retro-orbital bleeding underisofluran anaesthesia and 7 h later on sacrificed animals. Plasma wasseparated from blood using low speed centrifugation and CETP activitywas measured in plasma using the radioactive CETP activity assay asdescribed above except that diluted plasma replaced LPDS. In vivo CETPinhibition was expressed as CETP activity remaining in the plasma oftreated animals as compared to plasma CETP activity of placebo treatedanimals.

Efficacy of compounds in modulating plasma lipid levels can bedetermined in hamsters after 7 days of daily administration ofcompounds. Male hamsters are acclimated for 3-4 days to receive food asa paste made of 10 g chow and 10 g water per day. Compounds are thenmixed within this paste and a portion containing the proper amount ofcompounds is given every morning for 7 days. Alternatively compounds canbe given by oral gavage using the proper vehicle. Blood is taken beforecompound treatment by retro-orbital bleeding and at the end of thetreatment on sacrificed animals. Plasma is separated from blood by lowspeed centrifugation and selected organs are taken (e.g liver, fat,brain, etc.). Effects of compounds on plasma lipid levels are determinedby measuring total cholesterol, HDL-cholesterol, LDL-cholesterol andtriglyceride using colorimetric enzymatic assays (Roche Diagnostic GmbH,Mannheim, Germany). HDL-C, LDL-C and VLDL-C are e.g., quantified usingsize exclusion chromatography on superpose-6 column using SMART™ system(Pharmacia). Lipoprotein distribution is calculated assuming a Gaussiandistribution for each peak, using a non-linear, least-squarescurve-fitting procedure to calculate the area under the curve. Plasmasamples are also used to quantify CETP activity as described above.Compound concentration is also determined in plasma and selected tissuesas liver, fat, heart, muscle and brain.

Efficacy of compounds in modulating plasma lipid levels was alsodetermined in cholesterol/fat fed hamsters. The protocol is identical asdescribed above except that animals are fed with chow diet enriched with10% (w/w) saturated fat and 0.05% (w/w) cholesterol. Animals receivedthis high fat diet 2 weeks before starting compound administration andcontinued this diet throughout the study. The 2 weeks pre-treatmentinduced an increase in plasma cholesterol and triglyceride levelsallowing a better assessment of LDL-C and triglyceride lowering.Efficacy of compounds in its ability to acutely raise HDL-C can beassessed in cynomolgus monkeys. Animals are fed with standard primatemaintenance diet. Compounds are formulated with appropriate vehicle andadministered to animals by oral gavage. Blood is taken before and atseveral time-points after compound administration (usually 30 min, 1 h,2 h, 4 h, 7 h and 24 h). Plasma is separated from blood by low speedcentrifugation and CETP activity and plasma lipids are quantified.Compound potency and efficacy can be assessed by measuring the HDL-Cincrease after this single-dose administration. In such pharmacodynamicmodel the extent together with the kinetics of the pharmacologic effectcan be assessed.

The compounds of formula I and their pharmaceutically acceptable saltsand esters can be used as medicaments, e.g. in the form ofpharmaceutical preparations for enteral, parenteral or topicaladministration. They can be administered, e.g., perorally, e.g. in theform of tablets, coated tablets, dragées, hard and soft gelatinecapsules, solutions, emulsions or suspensions, rectally, e.g. in theform of suppositories, parenterally, e.g. in the form of injectionsolutions or infusion solutions, or topically, e.g. in the form ofointments, creams or oils.

The production of the pharmaceutical preparations can be effected in amanner which will be familiar to any person skilled in the art bybringing the described compounds of formula I and their pharmaceuticallyacceptable, into a galenical administration form together with suitable,non-toxic, inert, therapeutically compatible solid or liquid carriermaterials and, if desired, usual pharmaceutical adjuvants.

Suitable carrier materials are not only inorganic carrier materials, butalso organic carrier materials. Thus, e.g., lactose, corn starch orderivatives thereof, talc, stearic acid or its salts can be used ascarrier materials for tablets, coated tablets, dragées and hard gelatinecapsules. Suitable carrier materials for soft gelatine capsules are,e.g., vegetable oils, waxes, fats and semi-solid and liquid polyols(depending on the nature of the active ingredient no carriers are,however, required in the case of soft gelatine capsules). Suitablecarrier materials for the production of solutions and syrups are, e.g.,water, polyols, sucrose, invert sugar and the like. Suitable carriermaterials for injection solutions are, e.g., water, alcohols, polyols,glycerol and vegetable oils. Suitable carrier materials forsuppositories are, e.g., natural or hardened oils, waxes, fats andsemi-liquid or liquid polyols. Suitable carrier materials for topicalpreparations are glycerides, semi-synthetic and synthetic glycerides,hydrogenated oils, liquid waxes, liquid paraffins, liquid fattyalcohols, sterols, polyethylene glycols and cellulose derivatives.

Usual stabilizers, preservatives, wetting and emulsifying agents,consistency-improving agents, flavour-improving agents, salts forvarying the osmotic pressure, buffer substances, solubilizers, colorantsand masking agents and antioxidants come into consideration aspharmaceutical adjuvants.

The dosage of the compounds of formula I can vary within wide limitsdepending on the disease to be controlled, the age and the individualcondition of the patient and the mode of administration, and will, ofcourse, be fitted to the individual requirements in each particularcase. For adult patients a daily dosage of about 1 mg to about 1000 mg,especially about 1 mg to about 100 mg, comes into consideration.Depending on the dosage it is convenient to administer the daily dosagein several dosage units.

The pharmaceutical preparations conveniently contain about 0.1-500 mg,e.g., 0.5-100 mg, of a compound of formula I.

The following examples serve to illustrate the present invention in moredetail. They are, however, not intended to limit its scope in anymanner.

EXAMPLE A Film Coated Tablets

Ingredients Per tablet Kernel: Compound of formula (I) 10.0 mg  200.0mg  Microcrystalline cellulose 23.5 mg  43.5 mg  Lactose hydrous 60.0mg  70.0 mg  Povidone K30 12.5 mg  15.0 mg  Sodium starch glycolate 12.5mg  17.0 mg  Magnesium stearate 1.5 mg 4.5 mg (Kernel Weight) 120.0 mg 350.0 mg  Film Coat: Hydroxypropyl methyl cellulose 3.5 mg 7.0 mgPolyethylene glycol 6000 0.8 mg 1.6 mg Talc 1.3 mg 2.6 mg Iron oxide(yellow) 0.8 mg 1.6 mg Titanium dioxide 0.8 mg 1.6 mg

The active ingredient is sieved and mixed with microcrystallinecellulose and the mixture is granulated with a solution ofpolyvinylpyrrolidone in water. The granulate is mixed with sodium starchglycolate and magnesium stearate and compressed to yield kernels of 120or 350 mg respectively. The kernels are lacquered with an aqueoussolution/suspension of the above mentioned film coat.

EXAMPLE B Capsules

Ingredients Per capsule Compound of formula (I) 25.0 mg Lactose 150.0mg  Maize starch 20.0 mg Talc  5.0 mg

The components are sieved and mixed and filled into capsules of size 2.

EXAMPLE C Injection Solutions

Compound of formula (I) 3.0 mg Gelatin 150.0 mg Phenol 4.7 mg Sodiumcarbonate to obtain a final pH of 7 Water for injection solutions ad 1.0ml

EXAMPLE D Soft Gelatin Capsules

Capsule contents Compound of formula (I) 5.0 mg Yellow wax 8.0 mgHydrogenated Soya bean oil 8.0 mg Partially hydrogenated plant oils 34.0mg Soya bean oil 110.0 mg Weight of capsule contents 165.0 mg Gelatincapsule Gelatin 75.0 mg Glycerol 85% 32.0 mg Karion 83 8.0 mg (drymatter) Titanium dioxide 0.4 mg Iron oxide yellow 1.1 mg

The active ingredient is dissolved in a warm melting of the otheringredients and the mixture is filled into soft gelatin capsules ofappropriate size. The filled soft gelatin capsules are treated accordingto the usual procedures.

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein: R¹, R², R⁴ andR⁵ are independently hydrogen, C₁-C₆alkyl, C₁-C₆alkoxy or halogen; R³ isselected from the group consisting of: (1) C₃-C₆alkyl, (2)halogen-C₁-C₆alkyl, (3) C₃-C₆cycloalkyl optionally substituted byhalogen or alkoxy, (4) Si(C₁-C₆alkyl)₃, (5) —OR¹², wherein R¹² is (a)C₁-C₆alkyl optionally substituted by halogen, hydroxy, COOC₁-C₆alkyl,C₃-C₆cycloalkyl or phenyl which phenyl is optionally substituted byhalogen or cyano, (b) halogen-C₁-C₆alkyl, (c) C₃-C₆cycloalkyl, (d)phenyl, (e) benzyl optionally substituted by halogen or cyano, or (f)S(O)₂-C₁-C₆alkyl, and (6) pentafluorosulfuranyl; or R² and R³ takentogether with the carbon atoms they are attached to form a 5- or6-membered carbocyclic ring or a 5- or 6-membered heterocyclic ringcontaining one or two heteroatoms selected from N, O or S; R⁶ ishydrogen or C₁-C₆alkyl; R⁷ and R⁸ are independently hydrogen,C₁-C₆alkyl, hydroxy or halogen; R⁹ is selected from the group consistingof: (1) hydrogen, (2) C₁-C₆alkyl, (3) C₂-C₆alkenyl, (4)halogen-C₁-C₆alkyl, (5) heterocyclyl, (6) heteroaryl, (7) phenyl, (8)naphthyl, and (9) —NR¹⁴R¹⁵, wherein R¹⁴ and R¹⁵ independently arehydrogen, C₁-C₆alkyl or phenyl optionally substituted by halogen;wherein said heteroaryl or phenyl is optionally substituted by: (a)halogen, (b) C₁-C₆alkyl optionally substituted by halogen, (c)C₁-C₆alkoxy optionally substituted by halogen or (d) phenyl R¹⁰ and R¹¹are independently selected from the group consisting of: (1) hydrogen,(2) halogen, (3) C₁-C₆alkyl optionally substituted by hydroxy, (4) —CORwherein R is C₁-C₆alkyl optionally substituted by halogen, C₁-C₆alkoxy,or C₃-C₆cycloalkyl, (5) —CH₂—COO—CH₂CH₃, —CH₂—COOH, or —CH₂—CH₂—COOH,(6) S(O)₂—C₁-C₆alkyl, (7) C₃-C₆cycloalkyl, (8) cyano, and (9) phenyl; ortogether R¹⁰ and R¹¹ are C₁-C₆alkylene; A is CR¹⁷ or N, wherein R¹⁷ ishydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy or C₂-C₆alkenyl; B is CR¹⁸ orN, wherein R¹⁸ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy orC₂-C₆alkenyl; D is CR¹⁹ or N, wherein R¹⁹ is hydrogen, halogen,C₁-C₆alkyl, C₁-C₆alkoxy, C₂-C₆alkenyl or phenyl; and E is CR²⁰ or N,wherein R²⁰ is hydrogen, halogen, C₁-C₆alkyl, C₁-C₆alkoxy orC₂-C₆alkenyl; or alternatively, E is CR²⁰ and -A-B-D- is —N—O—,—NR²¹—N—, —S—N—, —S—CH— or —CH—S—, wherein R²¹ is hydrogen, halogen,C₁-C₆alkyl, C₁-C₆alkoxy or C₂-C₆alkenyl; or E is N and -A-B-D- is —N—O—,—S—N—, —S—CH—, —CH—CH— or —CH—S—; or E is S and -A-B-D- is —CH—CH—; andn is 1, 2 or
 3. 2. A compound of claim 1 wherein R³ is a C₃-C₆alkyl,halogen-C₁-C₆alkyl, or C₃-C₆cycloalkyl.
 3. A compound of claim 1 whereinR³ is a C₃-C₆alkyl or halogen-C₁-C₆alkyl wherein the halogen is fluoro.4. A compound of claim 1 wherein R⁹ is: (1) heteroaryl which isunsubstituted or substituted by one to five substituents selected fromthe group consisting of halogen, C₁-C₆alkyl, halogen-C₁-C₆alkyl andphenyl, or (2) phenyl which is unsubstituted or substituted by one tofive substituents selected from the group consisting of halogen,C₁-C₆alkyl, halogen-C₁-C₆alkyl and halogen-C₁-C₆alkoxy.
 5. A compound ofclaim 1 wherein R¹⁰ is hydrogen or a C₁-C₆alkyl.
 6. A compound of claim1 wherein R¹¹ is hydrogen or C₁-C₆alkyl.
 7. A compound of claim 1wherein E is CR²⁰.
 8. A compound of claim 1 wherein E is N.
 9. Acompound of claim 1 wherein E is S and -A-B-D- is —CH—CH—.
 10. A processfor the production of a compound of formula I according to claim 1 whichprocess comprises reacting an acid derivative, a compound of formula II

wherein R³³ is hydrogen, Li, Na, K or C₁-C₆alkyl; and R¹⁰, R¹¹, A, B, Dand E have the meanings as defined in claim 1; with a secondary aminederivative, a compound of formula III

wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹ and n have the meanings asdefined in claim 1 and optionally converting the resulting compound intoa pharmaceutically acceptable salt.
 11. A pharmaceutical compositioncomprising a compound according to claim 1 and a pharmaceuticallyacceptable carrier, adjuvant, or mixtures thereof.
 12. A compound ofclaim 1 selected from the group consisting of:5-chloro-N-(4-cyclopentyl-benzyl)-2-isopropylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-butyl-benzyl)-N-2-(3,4-dichloro-phenyl)-ethyl-2-methylamino-nicotinamide;6-methyl-3-methylamino-pyridine-2-carboxylic acid[2-(4-chloro-phenyl)-ethyl]-(4-cyclobutyl-benzyl)-amide;N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-5-ethyl-2-methylamino-nicotinamide;N-(4-tert-butylbenzyl)-2-chloro-N-[2-(3,4-dichlorophenyl)-ethyl]-3-fluoro-6-methylaminobenzamide;2-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-cyclopropyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;(2-{(4-tert-Butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)-aceticacid;5-Chloro-2-methylamino-N-[4-(3,3,3-trifluoro-2-hydroxy-propoxy)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-(3-hydroxy-propylamino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;3-(2-{(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)-propionicacid;2-Amino-3-bromo-N-(4-tert-butyl-benzyl)-5-methyl-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-3-chloro-5-methyl-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-(cyanomethyl-amino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(2-chloro-pyridin-4-yl)-ethyl]-amide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(2-chloro-pyridin-4-yl)-ethyl]-2-methylamino-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(2-chloro-pyridin-4-yl)-ethyl]-2-methylamino-benzamide;5-Chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2-isopropylamino-N-(4-pentafluoroethyl-benzyl)-benzamide;5-Chloro-2-isopropylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2-isopropylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide;5-Chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-isopropylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide;5-Chloro-2-isopropylamino-N-(4-pentafluoroethyl-benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(4-trifluoromethyl-pyridin-2-yl)-ethyl]-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(4-trifluoromethyl-pyridin-2-yl)-ethyl]-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(5-trifluoromethyl-pyridin-2-yl)-ethyl]-amide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(5-trifluoromethyl-pyridin-2-yl)-ethyl]-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(6-trifluoromethyl-pyridin-2-yl)-ethyl]-amide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(6-trifluoromethyl-pyridin-2-yl)-ethyl]-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(6-trifluoromethyl-pyridin-2-yl)-ethyl]-benzamide;5-Chloro-N-(4-cyclobutyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-isopropylamino-benzamide;5-Chloro-N-(4-cyclobutyl-benzyl)-2-isopropylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(5-chloro-pyridin-2-yl)-ethyl]-2-methylamino-benzamide;5-Chloro-N-[4-(1-fluoro-cyclobutyl)-benzyl]-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-N-[4-(1-fluoro-cyclobutyl)-benzyl]-2-methylamino-benzamide;5-Chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-N-[4-(1-methoxy-cyclobutyl)-benzyl]-2-methylamino-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-cyclopropylamino-N-[2-(3,4-dichloro-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-cyclopropylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-cyclobutyl-benzyl)-2-cyclopropylamino-5-trifluoromethyl-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-cyclobutyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-ethylamino-benzamide;5-Chloro-N-(4-cyclobutyl-benzyl)-2-ethylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-cyclopentyl-benzyl)-2-ethylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-cyclobutyl-benzyl)-2-ethylamino-N-[2-(4-fluoro-3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-cyclopentyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-ethylamino-benzamide;5-Chloro-N-(4-cyclopentyl-benzyl)-2-ethylamino-N-[2-(4-fluoro-3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro-3-trifluoromethyl-pyrazol-1-yl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(3-phenyl-pyrazol-1-yl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethyl]-2-methylamino-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro-3-methyl-5-trifluoromethyl-pyrazol-1-yl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro-5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(4-trifluoromethyl-imidazol-1-yl)-ethyl]-nicotinamide;and a pharmaceutically acceptable salt thereof.
 13. A compound of claim1 selected from the group consisting of:N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(4-trifluoromethyl-imidazol-1-yl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(3-trifluoromethyl-pyrazol-1-yl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(5-trifluoromethyl-pyrazol-1-yl)-ethyl]-benzamide;3-Ethylamino-5-methyl-isoxazole-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;1,3-Dimethyl-5-methylamino-1H-pyrazole-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;5-Ethylamino-3-methyl-isothiazole-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;3-Methyl-5-methylamino-isothiazole-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;3-Methyl-5-methylamino-isothiazole-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;5-Cyclopropylamino-3-methyl-isothiazole-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;5-Cyclopropylamino-3-methyl-isothiazole-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;5-Isopropylamino-3-methyl-isothiazole-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;5-Isopropylamino-3-methyl-isothiazole-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;5-Cyclopropylamino-thiazole-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;2-Methylamino-thiophene-3-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;3-Methylamino-thiophene-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;3-Methylamino-thiophene-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;4-Methylamino-thiophene-3-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;4-Methylamino-thiophene-3-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;4-Acetylamino-N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-nicotinamide;4-Acetylamino-N-(4-tert-butyl-benzyl)-N-[2-(4-chloro-3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;4-Acetylamino-N-(4-tert-butyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;3-Amino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;3-Acetylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;2-Amino-N-(4-tert-butyl-benzyl)-N-[2-(4-chloro-3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;2-Amino-N-(4-tert-butyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;3-Methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;3-Amino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;3-Methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;3-Amino-6-methyl-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;6-Methyl-3-methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl-2-ethylamino-nicotinamide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl-2-dimethylamino-nicotinamide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-4-methylamino-nicotinamide;N-(4-tert-Butyl-benzyl)-2-cyclopropylamino-N-[2-(3,4-dichloro-phenyl)-ethyl]-nicotinamide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-4-ethylamino-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-nicotinamide;5-Bromo-N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-nicotinamide;5-Bromo-N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-ethylamino-nicotinamide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-(2-hydroxy-ethylamino)-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-ethylamino-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-cyclopropylamino-N-[2-(3,4-dichloro-phenyl)-ethyl]-nicotinamide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-5-fluoro-2-methylamino-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-(2-hydroxy-ethylamino)-nicotinamide;3-Amino-N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-isonicotinamide;3-Amino-pyrazine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-3-methylamino-isonicotinamide;3-Methylamino-pyrazine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-ethylamino-5-fluoro-nicotinamide;N-(4-tert-Butyl-benzyl)-2-cyclopropylamino-N-[2-(3,4-dichloro-phenyl)-ethyl]-5-fluoro-nicotinamide;4-Amino-pyrimidine-5-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide; and apharmaceutically acceptable salt thereof.
 14. A compound of claim 1selected from the group consisting of:2-Amino-N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-6-methyl-nicotinamide;4-Methylamino-pyrimidine-5-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-6-methyl-2-methylamino-nicotinamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;5-Chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methyl-amino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide;5-Chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2-methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide;5-Chloro-2-methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;N-Butyl-N-(4-tert-butyl-benzyl)-5-chloro-2-methylamino-nicotinamide;5-Chloro-2-cyclopropylamino-N-[2-(3,4-dichloro-phenyl)-ethyl]-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide;5-Chloro-2-cyclopropylamino-N-[2-(4-fluoro-phenyl)-ethyl]-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-cyclopropylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;5-Chloro-N-(4-cyclobutyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-nicotinamide;5-Chloro-N-(4-cyclopentyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-nicotinamide;5-Chloro-2-cyclopropylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;5-Chloro-N-(4-cyclobutyl-benzyl)-2-cyclopropylamino-N-[2-(3,4-dichloro-phenyl)-ethyl]-nicotinamide;5-Amino-pyrimidine-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;5-Methylamino-pyrimidine-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid[2-(3,4-dichloro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-amide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid[2-(4-fluoro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-amide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;6-Chloro-3-methylamino-pyridine-2-carboxylic acidbutyl-(4-tert-butyl-benzyl)-amide;6-Chloro-3-cyclopropylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;6-Chloro-3-cyclopropylamino-pyridine-2-carboxylic acid[2-(3,4-dichloro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-amide;6-Chloro-3-cyclopropylamino-pyridine-2-carboxylic acid[2-(4-fluoro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-amide;6-Chloro-3-cyclopropylamino-pyridine-2-carboxylic acid[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;6-Chloro-3-methylamino-pyridazine-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;5-Fluoro-N-[2-(4-fluoro-phenyl)-ethyl]-2-methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide;N-(4-Cyclobutyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-ethylamino-5-fluoro-nicotinamide;6-Chloro-3-methylamino-pyridazine-4-carboxylic acid[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;6-Chloro-3-methylamino-pyridazine-4-carboxylic acid(4-cyclobutyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;5-Bromo-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide;5-Bromo-N-(4-cyclobutyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-nicotinamide;5-Chloro-N-(4-cyclobutyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;6-Methoxy-3-methylamino-pyridazine-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;2-Amino-N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-nicotinamide;6-Chloro-3-methylamino-pyridazine-4-carboxylic acid[2-(3,4-dichloro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-amide;2-Ethylamino-5-fluoro-N-[2-(4-fluoro-phenyl)-ethyl]-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide;3-Methylamino-pyridazine-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-5-methyl-2-methylamino-nicotinamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-nicotinamide;5-Chloro-N-(4-cyclopropyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-(4-cyclopropyl-benzyl)-2-methylamino-nicotinamide;(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-ethylamino-5-methyl-nicotinamide;5-Chloro-N-(4-cyclopropyl-benzyl)-2-ethylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid[2-(4-chloro-phenyl)-ethyl]-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-amide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-cyclopropyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid[2-(4-chloro-phenyl)-ethyl]-(4-cyclopropyl-benzyl)-amide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-5-phenyl-nicotinamide;and a pharmaceutically acceptable salt thereof.
 15. A compound of claim1 selected from the group consisting of:3-Amino-6-methyl-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;3-Amino-6-methyl-pyrazine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;3-Amino-6-chloro-pyrazine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;6-Chloro-3-methylamino-pyrazine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;6-Methyl-3-methylamino-pyrazine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;6-Chloro-3-ethylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;6-Chloro-3-ethylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;N-(4-tert-Butyl-benzyl)-2-chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-5-methylamino-isonicotinamide;N-(4-tert-Butyl-benzyl)-2-chloro-5-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-isonicotinamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-phenethyl-amide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid[2-(3,4-dichloro-phenyl)-ethyl]-(4-(pentafluorothio)-benzyl)-amide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-5-vinyl-nicotinamide;2-Chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-5-methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-isonicotinamide;5-Amino-2-chloro-pyrimidine-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;2-Chloro-5-methylamino-pyrimidine-4-carboxylic acid(4-tert-butyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;5-Chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-N-(4-isopropyl-benzyl)-2-methylamino-nicotinamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-cyclobutyl-benzyl)-[2-(3,4-dichloro-phenyl)-ethyl]-amide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-cyclobutyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;2-Chloro-N-(4-cyclobutyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-5-methylamino-isonicotinamide;2-Chloro-N-(4-cyclobutyl-benzyl)-5-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-isonicotinamide;2-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-5-methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-isonicotinamide;2-Chloro-5-methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-isonicotinamide;5-Chloro-N-[4-(1-fluoro-cyclopropyl)-benzyl]-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;5-Chloro-N-[4-(1-fluoro-cyclopropyl)-benzyl]-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-isopropyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;5-Chloro-N-(4-isopropyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;6-Chloro-3-methylamino-pyrazine-2-carboxylic acid(4-isopropyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;6-Chloro-3-methylamino-pyrazine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-isopropyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;2-Chloro-N-(4-isopropyl-benzyl)-5-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-isonicotinamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-[4-(1-fluoro-cyclopropyl)-benzyl]-2-methylamino-benzamide;5-Chloro-N-(4-isopropyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-nicotinamide;5-Chloro-N-(4-isopropyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-(4-isopropyl-benzyl)-2-methylamino-nicotinamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-(4-isopropyl-benzyl)-2-methylamino-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-(2,2-difluoro-2-phenyl-ethyl)-amide;N-(4-tert-Butyl-benzyl)-5-chloro-N-{2-[(4-chloro-phenyl)-methyl-amino]-ethyl}-2-methylamino-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-{2-[(4-chloro-phenyl)-methyl-amino]-ethyl}-2-methylamino-benzamide;5-Chloro-2-methylamino-N-(4-pentafluoroethyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-pentafluoroethyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;5-Chloro-2-methylamino-N-(4-pentafluoroethyl-benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-pentafluoroethyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-amide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-N-(4-pentafluoroethyl-benzyl)-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid[2-(4-chloro-phenyl)-ethyl]-(4-pentafluoroethyl-benzyl)-amide;5-Chloro-N-[2-(3-methoxy-phenyl)-ethyl]-2-methylamino-N-(4-pentafluoroethyl-benzyl)-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid[2-(3-methoxy-phenyl)-ethyl]-(4-pentafluoroethyl-benzyl)-amide;5-Chloro-2-methylamino-N-(4-pentafluoroethyl-benzyl)-N-(2-p-tolyl-ethyl)-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-pentafluoroethyl-benzyl)-(2-p-tolyl-ethyl)-amide;5-Chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2-methylamino-N-(4-pentafluoroethyl-benzyl)-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid[2-(4-fluoro-phenyl)-ethyl]-(4-pentafluoroethyl-benzyl)-amide;5-Chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2-methylamino-N-(4-pentafluoroethyl-benzyl)-nicotinamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-N-(4-pentafluoroethyl-benzyl)-nicotinamide;5-Chloro-2-methylamino-N-(4-pentafluoroethyl-benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-nicotinamide;5-Chloro-N-[2-(3-methoxy-phenyl)-ethyl]-2-methylamino-N-(4-pentafluoroethyl-benzyl)-nicotinamide;5-Chloro-2-methylamino-N-(4-pentafluoroethyl-benzyl)-N-(2-p-tolyl-ethyl)-nicotinamide;and a pharmaceutically acceptable salt thereof.
 16. A compound of claim1 selected from the group consisting of:N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro-phenylamino)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-(2-naphthalen-2-yl-ethyl)-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(4-chloro-phenylamino)-ethyl]-amide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-(2-naphthalen-2-yl-ethyl)-amide;5-Chloro-2-methylamino-N-(4-pentafluoroethyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;2-Chloro-5-methylamino-N-(4-pentafluoroethyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-isonicotinamide;2-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-5-methylamino-N-(4-pentafluoroethyl-benzyl)-isonicotinamide;5-Chloro-2-ethylamino-N-(4-pentafluoroethyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-ethylamino-N-(4-pentafluoroethyl-benzyl)-benzamide;6-Chloro-3-methylamino-pyrazine-2-carboxylic acid(4-cyclobutyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amide;6-Chloro-3-methylamino-pyrazine-2-carboxylic acid(4-cyclobutyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;6-Chloro-3-methylamino-pyrazine-2-carboxylic acid[2-(4-chloro-phenyl)-ethyl]-(4-cyclobutyl-benzyl)-amide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid[2-(4-chloro-phenyl)-ethyl]-(4-cyclobutyl-benzyl)-amide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-cyclobutyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amide;3-Amino-6-methyl-pyridine-2-carboxylic acid[2-(4-chloro-phenyl)-ethyl]-(4-cyclobutyl-benzyl)-amide;3-Amino-6-methyl-pyridine-2-carboxylic acid(4-cyclobutyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amide;3-Amino-6-methyl-pyridine-2-carboxylic acid(4-cyclobutyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;6-Methyl-3-methylamino-pyridine-2-carboxylic acid(4-cyclobutyl-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amide;6-Methyl-3-methylamino-pyridine-2-carboxylic acid(4-cyclobutyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;N-(4-tert-Butyl-benzyl)-5-chloro-3-fluoro-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-3-fluoro-2-methylamino-benzamide;2-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-3-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(4-fluoro-phenyl)-ethyl]-3-iodo-benzamide;N-(4-tert-Butyl-benzyl)-2,3-dichloro-6-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;6-Amino-N-(4-tert-butyl-benzyl)-2,3-dichloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-2,3-dichloro-6-(cyclopropanecarbonyl-amino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;6-Acetylamino-N-(4-tert-butyl-benzyl)-2,3-dichloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-2,3-dichloro-6-propionylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;6-Amino-N-(4-tert-butyl-benzyl)-2,3-dichloro-N-[2-(3-difluoromethoxy-phenyl)-ethyl]-benzamide;6-Acetylamino-N-(4-tert-butyl-benzyl)-2,3-dichloro-N-[2-(3-difluoromethoxy-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-2,3-dichloro-N-[2-(3-difluoromethoxy-phenyl)-ethyl]-6-propionylamino-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-6-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-6-methyl-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Acetylamino-N-(4-tert-butyl-benzyl)-6-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Acetylamino-N-(4-tert-butyl-benzyl)-6-methyl-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;2-Acetylamino-N-butyl-N-(4-tert-butyl-benzyl)-5-chloro-benzamide;2-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;6-Amino-N-(4-tert-butyl-benzyl)-3-chloro-2-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-3-chloro-6-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-2,3-dichloro-6-(2,2,2-trifluoro-acetylamino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;6-Acetylamino-N-(4-tert-butyl-benzyl)-3-chloro-2-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(2-chloro-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-chloro-phenyl)-ethyl]-benzamide;2-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(2-chloro-phenyl)-ethyl]-benzamide;2-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-chloro-phenyl)-ethyl]-benzamide;2-Acetylamino-N-(4-tert-butyl-benzyl)-3-chloro-6-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(4-chloro-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(4-methoxy-phenyl)-ethyl]-benzamide;2-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(4-chloro-phenyl)-ethyl]-benzamide;2-Acetylamino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(4-methoxy-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-3-chloro-6-fluoro-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-3,5-dichloro-6-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Acetylamino-5-chloro-N-[(R)-2-(4-chloro-phenyl)-2-hydroxy-ethyl]-N-(4-cyclopropyl-benzyl)-benzamide;2-Acetylamino-N-(4-tert-butyl-benzyl)-3,5-dichloro-6-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-3,5-dichloro-N-[(R)-2-(4-chloro-phenyl)-2-hydroxy-ethyl]-N-(4-cyclopropyl-benzyl)-6-fluoro-benzamide;6-Acetylamino-2,3-dichloro-N-[(R)-2-(4-chloro-phenyl)-2-hydroxy-ethyl]-N-(4-cyclopropyl-benzyl)-benzamide;2-Acetylamino-3,5-dichloro-N-[(R)-2-(4-chloro-phenyl)-2-hydroxy-ethyl]-N-(4-cyclopropyl-benzyl)-6-fluoro-benzamide;and a pharmaceutically acceptable salt thereof.
 17. A compound of claim1 selected from the group consisting of:2-Acetylamino-5-chloro-N-(4-cyclopropyl-benzyl)—N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;2-Acetylamino-5-chloro-N-(4-cyclopropyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-3,5-dichloro-N-(4-cyclopropyl-benzyl)-6-fluoro-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;2-Amino-3,5-dichloro-N-(4-cyclopropyl-benzyl)-6-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;6-Acetylamino-2,3-dichloro-N-(4-cyclopropyl-benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;6-Acetylamino-2,3-dichloro-N-(4-cyclopropyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-3,5-dichloro-N-(2-chloro-4-cyclopropyl-benzyl)-6-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Acetylamino-3,5-dichloro-N-(2-chloro-4-cyclopropyl-benzyl)-6-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Acetylamino-3,5-dichloro-N-(4-cyclopropyl-benzyl)-6-fluoro-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;2-Acetylamino-3,5-dichloro-N-(4-cyclopropyl-benzyl)-6-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-5-chloro-N-(2-chloro-4-cyclopropyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Acetylamino-5-chloro-N-(2-chloro-4-cyclopropyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-cyclopropyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-2-(cyanomethyl-amino)-N-(4-cyclopropyl-benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;5-Chloro-2-(cyanomethyl-amino)-N-(4-cyclopropyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2,3-Dichloro-6-(cyanomethyl-amino)-N-(4-cyclopropyl-benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;2,3-Dichloro-N-(4-cyclopropyl-benzyl)-6-methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;2,3-Dichloro-6-(cyanomethyl-amino)-N-(4-cyclopropyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2,3-Dichloro-N-(4-cyclopropyl-benzyl)-6-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-cyclopropyl-benzyl)-2-ethylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-cyclopropyl-benzyl)-2-ethylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-ethylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-cyclopropyl-2-fluoro-benzyl)-2-ethylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-cyclopropyl-3-fluoro-benzyl)-2-ethylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;3,5-Dichloro-N-(4-cyclopropyl-benzyl)-2-fluoro-6-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Acetylamino-3,5-dichloro-N-(4-cyclopropyl-benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;3,5-Dichloro-N-(4-cyclopropyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;3,5-Dichloro-N-(4-cyclopropyl-benzyl)-2-ethylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;3,5-Dichloro-2-(cyanomethyl-amino)-N-(4-cyclopropyl-benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;3,5-Dichloro-2-(cyanomethyl-amino)-N-(4-cyclopropyl-benzyl)-6-fluoro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-(4-cyclopropyl-benzyl)-2-methylamino-benzamide;5-Chloro-N-(4-cyclopropyl-benzyl)-N-[2-(4-fluoro-phenyl)-ethyl]-2-methylamino-benzamide;(2-{(4-tert-Butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-carbamoyl}-4-chloro-phenylamino)-aceticacid ethyl ester;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-(4-cyclopropyl-benzyl)-2-ethylamino-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-(cyanomethyl-amino)-N-(4-cyclopropyl-benzyl)-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-(cyanomethyl-amino)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-(cyanomethyl-amino)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;5-Chloro-2-methylamino-N-(4-trifluoromethoxy-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-2-ethylamino-N-(4-trifluoromethoxy-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-ethylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-(cyanomethyl-amino)-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide;5-Chloro-2-(cyanomethyl-amino)-N-(4-trifluoromethoxy-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2-methylamino-N-(4-trifluoromethoxy-benzyl)-benzamide;5-Chloro-2-ethylamino-N-[2-(4-fluoro-phenyl)-ethyl]-N-(4-trifluoromethoxy-benzyl)-benzamide;5-Chloro-2-(cyanomethyl-amino)-N-[2-(4-fluoro-phenyl)-ethyl]-N-(4-trifluoromethoxy-benzyl)-benzamide;{4-Chloro-2-[[2-(4-fluoro-phenyl)-ethyl]-(4-trifluoromethoxy-benzyl)-carbamoyl]-phenylamino}-aceticacid ethyl ester;{4-Chloro-2-[[2-(4-fluoro-phenyl)-ethyl]-(4-trifluoromethoxy-benzyl)-carbamoyl]-phenylamino}-aceticacid;5-Chloro-N-(3-chloro-4-trifluoromethoxy-benzyl)-N-[2-(4-fluoro-phenyl)-ethyl]-2-methylamino-benzamide;5-Chloro-2-(cyanomethyl-amino)-N-(4-cyclobutyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(3-chloro-4-trifluoromethoxy-benzyl)-2-ethylamino-N-[2-(4-fluoro-phenyl)-ethyl]-benzamide;5-Chloro-N-(3-chloro-4-trifluoromethoxy-benzyl)-2-(cyanomethyl-amino)-N-[2-(4-fluoro-phenyl)-ethyl]-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-N-(4-trifluoromethoxy-benzyl)-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-ethylamino-N-(4-trifluoromethoxy-benzyl)-benzamide;5-Chloro-N-(4-cyclobutyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-(cyanomethyl-amino)-N-(4-trifluoromethoxy-benzyl)-benzamide;5-Chloro-N-[4-(1-methoxy-cyclopropyl)-benzyl]-2-methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;5-Chloro-2-ethylamino-N-[4-(1-methoxy-cyclopropyl)-benzyl]-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;5-Chloro-2-(cyanomethyl-amino)-N-[4-(1-methoxy-cyclopropyl)-benzyl]-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-cyclobutyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-cyclobutyl-benzyl)-2-ethylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;5-Chloro-2-(cyanomethyl-amino)-N-(4-cyclobutyl-benzyl)-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;N-(4-Benzyloxy-benzyl)-5-chloro-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;[4-({(5-Chloro-2-methylamino-benzoyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amino}-methyl)-phenoxy]-aceticacid methyl ester;N-(4-tert-Butyl-benzyl)-2,3-dichloro-N-[2-(4-chloro-phenyl)-ethyl]-6-methylamino-benzamide;and a pharmaceutically acceptable salt thereof.
 18. A compound of claim1 selected from the group consisting of:2,3-Dichloro-N-[2-(4-chloro-phenyl)-ethyl]-6-methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide;N-(4-tert-Butyl-benzyl)-2,3-dichloro-6-methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-2,3-dichloro-N-[2-(4-fluoro-phenyl)-ethyl]-6-methylamino-benzamide;5-Chloro-N-[4-(4-cyano-benzyloxy)-benzyl]-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-[4-(4-fluoro-benzyloxy)-benzyl]-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2,3-Dichloro-N-[4-(1-methoxy-cyclopropyl)-benzyl]-6-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-[4-(1-methoxy-cyclopropyl)-benzyl]-2-methylamino-benzamide;2,3-Dichloro-N-[2-(4-chloro-phenyl)-ethyl]-N-[4-(1-methoxy-cyclopropyl)-benzyl]-6-methylamino-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-amide;N-(4-tert-Butoxy-benzyl)-2,3-dichloro-N-[2-(4-chloro-phenyl)-ethyl]-6-methylamino-benzamide;N-(4-tert-Butoxy-benzyl)-5-chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-N-(4-trifluoromethyl-benzyl)-benzamide;2,3-Dichloro-N-[2-(4-chloro-phenyl)-ethyl]-6-methylamino-N-(4-trifluoromethyl-benzyl)-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-N-[4-(1,1,2,2-tetrafluoro-ethoxy)-benzyl]-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-N-(4-phenoxy-benzyl)-benzamide;2,3-Dichloro-N-[2-(4-chloro-phenyl)-ethyl]-6-methylamino-N-[4-(1,1,2,2-tetrafluoro-ethoxy)-benzyl]-benzamide;2,3-Dichloro-N-[2-(4-chloro-phenyl)-ethyl]-6-methylamino-N-(4-phenoxy-benzyl)-benzamide;5-Chloro-2-methylamino-N-[4-(3,3,3-trifluoro-2-hydroxy-propoxy)-benzyl]-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;Methanesulfonic acid4-({(5-chloro-2-methylamino-benzoyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amino}-methyl)-phenylester;N-(4-tert-Butoxy-benzyl)-5-chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-ethylamino-benzamide;N-(4-tert-Butoxy-benzyl)-5-chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-nicotinamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butoxy-benzyl)-[2-(4-chloro-phenyl)-ethyl]-amide;N-(4-tert-Butoxy-benzyl)-5-chloro-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butoxy-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-amide;N-(4-tert-Butoxy-benzyl)-5-chloro-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;5-Chloro-N-(4-cyclopropylmethoxy-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butoxy-benzyl)-5-chloro-2-methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butoxy-benzyl)-[2-(3-trifluoromethoxy-phenyl)-ethyl]-amide;N-(4-tert-Butoxy-benzyl)-5-chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2-methylamino-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butoxy-benzyl)-[2-(4-fluoro-phenyl)-ethyl]-amide;N-(4-tert-Butoxy-benzyl)-5-chloro-N-[2-(4-fluoro-phenyl)-ethyl]-2-methylamino-nicotinamide;N-(4-tert-Butoxy-benzyl)-5-chloro-2-methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-ethylamino-N-[2-(4-fluoro-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-ethylamino-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-3,5-dichloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-3,5-dimethyl-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-3,5-dibromo-N-(4-tert-butyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-5-methyl-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-5-iodo-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-5-bromo-N-(4-tert-butyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;3,5-Dibromo-N-(4-tert-butyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-3-bromo-N-(4-tert-butyl-benzyl)-5-iodo-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-5-bromo-N-(4-tert-butyl-benzyl)-3-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-3-chloro-5-iodo-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-N-[2-(3-fluoro-4-trifluoromethyl-phenyl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-N-[2-(2-fluoro-3-trifluoromethyl-phenyl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-N-[2-(3-chloro-2-fluoro-phenyl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-N-[2-(3-chloro-4-fluoro-phenyl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-N-[2-(3-difluoromethoxy-phenyl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-N-[2-(4-chloro-3-fluoro-phenyl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-ethylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-N-(4-tert-butyl-benzyl)-5-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-2-(cyanomethyl-amino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamideN-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3-chloro-4-fluoro-phenyl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(3-difluoromethoxy-phenyl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-(cyclopropylmethyl-amino)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;(2-{(4-tert-Butyl-benzyl)-[2-(3-trifluoromethyl-phenyl)-ethyl]-carbamoyl}-4-chloro-phenyl)-carbamicacid methyl ester;N-(4-tert-Butyl-benzyl)-5-chloro-2-isopropylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-3-chloro-2-fluoro-6-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;2-Amino-5-chloro-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-N-(4-trimethylsilanyl-benzyl)-benzamide;2-Amino-5-chloro-N-[2-(4-chloro-phenyl)-ethyl]-N-(4-trimethylsilanyl-benzyl)-benzamide;2-Amino-5-chloro-N-[2-(4-fluoro-phenyl)-ethyl]-N-(4-trimethylsilanyl-benzyl)-benzamide;2-Amino-5-chloro-N-[2-(3,4-dichloro-phenyl)-ethyl]-N-(4-trimethylsilanyl-benzyl)-benzamide;N-Butyl-N-(4-tert-butyl-benzyl)-2-methylamino-benzamide;N-(4-tert-Butyl-benzyl)-2,3-dichloro-6-methanesulfonylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methanesulfonylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;and a pharmaceutically acceptable salt thereof.
 19. A compound of claim1 selected from the group consisting of:N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;N-(4-tert-Butyl-benzyl)-2-chloro-5-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-isonicotinamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-methylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide;5-Chloro-N-[2-(4-chloro-phenyl)-ethyl]-2-ethylamino-N-[4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-benzyl]-benzamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;and a pharmaceutically acceptable salt thereof.
 20. A compound ofselected from the group consisting of:N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-((R)-2-hydroxymethyl-pyrrolidin-1-yl)-nicotinamide;N-(4-tert-Butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-2-pyrrolidin-1-yl-nicotinamide;2-Azetidin-1-yl-N-(4-tert-butyl-benzyl)-N-[2-(3,4-dichloro-phenyl)-ethyl]-nicotinamide;5-Chloro-2-methylamino-N-(4-methyl-benzyl)-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-ethyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-benzamide;5-Chloro-N-(4-ethyl-benzyl)-2-methylamino-N-[2-(3-trifluoromethyl-phenyl)-ethyl]-nicotinamide;N-(4-tert-Butyl-benzyl)-5-chloro-2-methylamino-N-(2-phenoxy-ethyl)-benzamide;6-Chloro-3-methylamino-pyridine-2-carboxylic acid(4-tert-butyl-benzyl)-(2-phenoxy-ethyl)-amide; and a pharmaceuticallyacceptable salt thereof.